Login Register Cart 0
Generic placeholder image

Current Drug Safety

Editor-in-Chief

ISSN (Print): 1574-8863
ISSN (Online): 2212-3911

Back
Journal Home About Journal Editorial Board Journal Insight Current Issue Volumes/Issues
Subscribe
Research Article

Comparative Efficacy and Safety Study of Darbepoetin Alfa versus Epoetin Alfa in Management of Anemia Associated with ESRD in Egyptian Hemodialysis Patients

Author(s): Nahla E. El-Ashmawy, Eman G. Khedr, Nahla S. Kotb, Fathi Salem and Amera O. Ibrahim*

Volume 17, Issue 3, 2022

Published on: 11 January, 2022

Page: [250 - 258] Pages: 9

DOI: 10.2174/1568009621666211123095129

Price: $65

Abstract

Background: Anemia is one of the most common complications of Chronic Kidney Disease (CKD). The vast majority of Egyptian CKD patients are interchangeably treated with Darbepoetin Alfa (DPA) and Epoetin Alfa (EPA) to achieve and maintain target hemoglobin levels. Our study aimed to compare the efficacy and safety of DPA versus EPA for managing anemia amongst Egyptian patients with CKD undergoing dialysis.

Methods: A multicenter, open label, randomized, prospective, parallel study was conducted. Patients with CKD undergoing dialysis with Hb level < 10 g/dl were enrolled. The primary efficacy endpoint was the change in hemoglobin concentration at the evaluation period (weeks 20-24). Prespecified adverse events of interest following administration, including blood transfusions requirement, blood pressure and hemoglobin excursions, the relationship between C - Reactive Protein (CRP) and hemoglobin, were assessed.

Results: Only 98 of 104 enrolled patients completed the study, fifty patients received EPA, and 48 patients received DPA. Our results showed that a significantly higher percentage of patients who achieved target Hb level ≥ 11 g/dL in DPA treated group vs. EPA as well as the meantime to achieve Hb level ≥ 10 g/dL was shorter in DPA treated group. Safety profiles of both treatments were similar. A negative correlation was observed between serum CRP and hemoglobin level in hemodialysis patients.

Conclusion: Our study showed that DPA was more effective and well tolerated in achieving and maintaining Hb levels with lower dosing frequency compared to EPA. Furthermore, CRP is recommended to be routinely measured where patients with higher CRP require high ESA doses.

Keywords: Darpepoetin alfa, epotein alfa, chronic kidney disease, C-reactive protein, hemodialysis, anemia.

« Previous Next »
Graphical Abstract

[1]
Coyne DW, Goldsmith D, Macdougall IC. New options for the anemia of chronic kidney disease. Kidney Int Suppl 2017; 7(3): 157-63.
[http://dx.doi.org/10.1016/j.kisu.2017.09.002] [PMID: 30675430]
[2]
Babitt JL, Lin HY. Mechanisms of anemia in CKD. J Am Soc Nephrol 2012; 23(10): 1631-4.
[http://dx.doi.org/10.1681/ASN.2011111078]
[3]
Alexander M, Kewalramani R, Agodoa I, Globe D. Association of anemia correction with health related quality of life in patients not on dialysis. Curr Med Res Opin 2007; 23(12): 2997-3008.
[http://dx.doi.org/10.1185/030079907X242502] [PMID: 17958944]
[4]
Rahman H, Jahan S, Begum A, Muinuddin G, Hossain M. Use of recombinant human erythropoietin in renal anemia in children. Bangabandhu Sheikh Mujib Med Univ J 2009; 2(1): 50-3.
[http://dx.doi.org/10.3329/bsmmuj.v2i1.3713]
[5]
Roger SD, Jassal SV, Woodward MC, Soroka S, McMahon LP. A randomised single-blind study to improve health-related quality of life by treating anaemia of chronic kidney disease with Aranesp® (darbepoetin alfa) in older people: STIMULATE. Int Urol Nephrol 2014; 46(2): 469-75.
[http://dx.doi.org/10.1007/s11255-013-0512-1] [PMID: 23982766]
[6]
McFarlane PA, Pisoni RL, Eichleay MA, Wald R, Port FK, Mendelssohn D. International trends in erythropoietin use and hemoglobin levels in hemodialysis patients. Kidney Int 2010; 78(2): 215-23.
[http://dx.doi.org/10.1038/ki.2010.108] [PMID: 20428102]
[7]
Rompas S, Goss T, Amanuel S, et al. Demonstrating value for biosimilars: A conceptual framework. Am Health Drug Benefits 2015; 8(3): 129-39.
[PMID: 26085901]
[8]
Locatelli F, Aljama P, Bárány P, et al. Revised European best practice guidelines for the management of anaemia in patients with chronic renal failure. Nephrol Dial Transplant 2004; 19(Suppl. 2): ii1-ii47.
[PMID: 15206425]
[9]
Egrie JC, Dwyer E, Browne JK, Hitz A, Lykos MA. Darbepoetin alfa has a longer circulating half-life and greater in vivo potency than recombinant human erythropoietin. Exp Hematol 2003; 31(4): 290-9.
[http://dx.doi.org/10.1016/S0301-472X(03)00006-7] [PMID: 12691916]
[10]
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): 741-7.
[http://dx.doi.org/10.1046/j.1523-1755.2001.060002741.x] [PMID: 11473657]
[11]
Fouad S. Cost Efectivness of darbepoetin alfa Versus epoetin alfa in the management of anemic patients with chronic kidney disease: Health insurance perspective. Value Health 2016; 19(7): 589.
[http://dx.doi.org/10.1016/j.jval.2016.09.1394]
[12]
Roger SD, Kolmakova E, Fung M, et al. Darbepoetin alfa once monthly corrects anaemia in patients with chronic kidney disease not on dialysis. Nephrology (Carlton) 2014; 19(5): 266-74.
[http://dx.doi.org/10.1111/nep.12214] [PMID: 24506498]
[13]
Alves MT, Vilaça SS, Carvalho Md, Fernandes AP, Dusse LM, Gomes KB. Resistance of dialyzed patients to erythropoietin. Rev Bras Hematol Hemoter 2015; 37(3): 190-7.
[http://dx.doi.org/10.1016/j.bjhh.2015.02.001] [PMID: 26041422]
[14]
El-Ghamry F, Nassar Y, El Sayed MA, et al. The relation between the levels of c-reactive protein and the response to erythropoietin in anemic patients on haemodialysis. AAMJ 2014.
[15]
Heidari B. C-reactive protein and other markers of inflammation in hemodialysis patients. Caspian J Intern Med 2013; 4(1): 611-6.
[PMID: 24009946]
[16]
Rossert J, Gassmann-Mayer C, Frei D, McClellan W. Prevalence and predictors of epoetin hyporesponsiveness in chronic kidney disease patients. Nephrol Dial Transplant 2007; 22(3): 794-800.
[http://dx.doi.org/10.1093/ndt/gfl716] [PMID: 17210593]
[17]
Ebied WM, Ahmed HA, Elbarbry FA. Production and analysis of a biosimilar erythropoietin in Egypt. Biosimilars 2014; 4: 11.
[18]
Chawla LS, Krishnan M. Causes and consequences of inflammation on anemia management in hemodialysis patients. Hemodial Int 2009; 13(2): 222-34.
[http://dx.doi.org/10.1111/j.1542-4758.2009.00352.x] [PMID: 19432697]
[19]
Al Saran K, Sabry A, Shalaby M, Al Sherbeiny S, Abdelkader M. Level of C-reactive protein in chronic hemodialysis patients: a comparative study between patients with non-infected catheters and arteriovenous fistula in a large Saudi hemodialysis center. Ther Apher Dial 2013; 17(1): 35-9.
[http://dx.doi.org/10.1111/j.1744-9987.2012.01116.x] [PMID: 23379491]
[20]
Jofré R, Rodriguez-Benitez P, López-Gómez JM, Pérez-Garcia R. Inflammatory syndrome in patients on hemodialysis. J Am Soc Nephrol 2006; 17(12)(Suppl. 3): S274-80.
[http://dx.doi.org/10.1681/ASN.2006080926] [PMID: 17130274]
[21]
McFarlane PA, Hillmer MP, Dacouris N. A change from subcutaneous to intravenous erythropoietin increases the cost of anemia therapy. Nephron Clin Pract 2007; 107(3): c90-6.
[http://dx.doi.org/10.1159/000108649] [PMID: 17890876]
[22]
Shahab MH, Saifullah Khan S. Erythropoietin administration for anemia due to chronic kidney disease - subcutaneous or intravenous, what do we know so far? Cureus 2020; 12(9): e10358.
[PMID: 33062481]
[23]
Kaufman JS, Reda DJ, Fye CL, et al. Subcutaneous compared with intravenous epoetin in patients receiving hemodialysis. N Engl J Med 1998; 339(9): 578-83.
[http://dx.doi.org/10.1056/NEJM199808273390902] [PMID: 9718376]
[24]
Wazny LD, Raymond CB, Sood AR, Eng A, Verrelli M. Cost analysis of an intravenous to subcutaneous epoetin α conversion. Am J Nephrol 2013; 38(6): 496-500.
[http://dx.doi.org/10.1159/000357052] [PMID: 24334854]
[25]
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): 860-73.
[http://dx.doi.org/10.1053/j.ajkd.2013.08.001] [PMID: 24054466]
[26]
Kliger AS, Foley RN, Goldfarb DS, et al. KDOQI US commentary on the 2012 KDIGO clinical practice guideline for anemia in CKD. Am J Kidney Dis 2013; 62(5): 849-59.
[http://dx.doi.org/10.1053/j.ajkd.2013.06.008] [PMID: 23891356]
[27]
Mikhail A, Brown C, Williams JA, et al. Renal association clinical practice guideline on anaemia of chronic kidney disease. BMC Nephrol 2017; 18(1): 345.
[http://dx.doi.org/10.1186/s12882-017-0688-1] [PMID: 29191165]
[28]
Stephens JM, Emerson LC, Spry LA, et al. Time savings of weekly versus three-times-per-week administration of erythropoiesis stimulating agents in United States dialysis patients. Curr Med Res Opin 2016; 32(2): 313-20.
[http://dx.doi.org/10.1185/03007995.2015.1123144] [PMID: 26583202]
[29]
Johansen KL, Finkelstein FO, Revicki DA, Gitlin M, Evans C, Mayne TJ. Systematic review and meta-analysis of exercise tolerance and physical functioning in dialysis patients treated with erythropoiesis-stimulating agents. Am J Kidney Dis 2010; 55(3): 535-48.
[http://dx.doi.org/10.1053/j.ajkd.2009.12.018] [PMID: 20133033]
[30]
Gandra SR, Finkelstein FO, Bennett AV, Lewis EF, Brazg T, Martin ML. Impact of erythropoiesis-stimulating agents on energy and physical function in nondialysis CKD patients with anemia: A systematic review. Am J Kidney Dis 2010; 55(3): 519-34.
[http://dx.doi.org/10.1053/j.ajkd.2009.09.019] [PMID: 20031287]
[31]
Locatelli F, Villa G, Messa P, et al. Efficacy and safety of once-weekly intravenous epoetin alfa in maintaining hemoglobin levels in hemodialysis patients. J Nephrol 2008; 21(3): 412-20.
[PMID: 18587731]
[32]
Palmer SC, Saglimbene V, Mavridis D, et al. Erythropoiesis-stimulating agents for anaemia in adults with chronic kidney disease: A network meta-analysis. Cochrane Database Syst Rev 2014; (12): CD010590.
[http://dx.doi.org/10.1002/14651858.CD010590.pub2] [PMID: 25486075]
[33]
Improving KD, Group GOKAW. Kdigo clinical practice guideline for anemia in chronic kidney disease. Kidney Int Suppl 2012; 2(4): 279-335.
[34]
Macdougall IC. An overview of the efficacy and safety of Novel Erythropoiesis Stimulating Protein (NESP). Nephrol Dial Transplant 2001; 16(Suppl. 3): 14-21.
[http://dx.doi.org/10.1093/ndt/16.suppl_3.14] [PMID: 11402086]
[35]
Rottembourg JB, Kpade F, Tebibel F, Dansaert A, Chenuc G. Stable hemoglobin in hemodialysis patients: Forest for the trees-a 12-week pilot observational study. BMC Nephrol 2013; 14: 243.
[http://dx.doi.org/10.1186/1471-2369-14-243] [PMID: 24180578]
[36]
Ishani A, Guo H, Gilbertson DT, et al. Time to target haemoglobin concentration (11 g/dl)- risk of hospitalization and mortality among incident dialysis patients. Nephrol Dial Transplant 2007; 22(8): 2247-55.
[http://dx.doi.org/10.1093/ndt/gfm374] [PMID: 17597082]
[37]
Mimura I, Tanaka T, Nangaku M. How the target hemoglobin of renal anemia should be? Nephron 2015; 131(3): 202-9.
[http://dx.doi.org/10.1159/000440849] [PMID: 26381503]
[38]
George M. Comparison of erythropoietin and darbepoetin in chronic kidney disease patientsin a tertiary care hospital. IJPPR 2017; 9(4): 191-205.
[39]
Amato L, Addis A, Saulle R, Trotta F, Mitrova Z, Davoli M. Comparative efficacy and safety in ESA biosimilars vs. originators in adults with chronic kidney disease: A systematic review and meta- analysis. J Nephrol 2018; 31(3): 321-32.
[http://dx.doi.org/10.1007/s40620-017-0419-5] [PMID: 28646375]
[40]
Vanrenterghem Y, Bárány 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): 2167-75.
[http://dx.doi.org/10.1046/j.1523-1755.2002.00657.x] [PMID: 12427142]
[41]
Winkelmayer WC, Chang TI, Mitani AA, et al. Longer-term outcomes of darbepoetin alfa versus epoetin alfa in patients with ESRD initiating hemodialysis: A quasi-experimental cohort study. Am J Kidney Dis 2015; 66(1): 106-13.
[http://dx.doi.org/10.1053/j.ajkd.2015.02.339] [PMID: 25943715]
[42]
Gluba-Brzózka A, Franczyk B, Olszewski R, Rysz J. The influence of inflammation on anemia in CKD patients. Int J Mol Sci 2020; 21(3): 725.
[http://dx.doi.org/10.3390/ijms21030725] [PMID: 31979104]
[43]
Heidari B, Fazli MR, Misaeid MAG, Heidari P, Hakimi N, Zeraati AA. A linear relationship between serum high-sensitive C-reactive protein and hemoglobin in hemodialysis patients. Clin Exp Nephrol 2015; 19(4): 725-31.
[http://dx.doi.org/10.1007/s10157-014-1048-0] [PMID: 25380841]

Rights & Permissions Print Cite
Article Metrics
50
1
Wayfinder Image
© 2024 Bentham Science Publishers | Privacy Policy