Comparison of the Therapeutic Effects of Two Recombinant Erythropoietin Beta, Biosimilar and Reference Formulations in Patients with Chronic Kidney Disease under Hemodialysis
Clinical Medicine Research
Volume 3, Issue 5, September 2014, Pages: 136-141
Received: Aug. 21, 2014;
Accepted: Sep. 3, 2014;
Published: Sep. 20, 2014
Views 3084 Downloads 474
Maria del Carmen Popoca-Martínez, Nephrology Department, General Hospital “Dr. Darío Fernández Fierro” ISSSTE, Av. Revolución 1182, Col. San José Insurgentes, México City 03900, Mexico
Julio Flores-Garnica, Nephrology Department, General Hospital “Dr. Darío Fernández Fierro” ISSSTE, Av. Revolución 1182, Col. San José Insurgentes, México City 03900, Mexico
Odette Díaz-Avendaño, Nephrology Department, General Hospital “Dr. Darío Fernández Fierro” ISSSTE, Av. Revolución 1182, Col. San José Insurgentes, México City 03900, Mexico
Emmanuel Canales-Vázquez, Clinical Research Department, Laboratorios PISA SA de CV. Miguel Ángel de Quevedo 555, Colonia Romero De Terreros, México City 04310 Mexico
Raúl Meixueiro-Montes De Oca, Clinical Research Department, Laboratorios PISA SA de CV. Miguel Ángel de Quevedo 555, Colonia Romero De Terreros, México City 04310 Mexico
Anemia is common in patients with chronic kidney diseases under hemodialysis and it’s managed with recombinant erythropoietin formulation. The objective of the study is to compare the safety and efficacy of two recombinant erythropoietin formulations in patients undergoing hemodialysis with chronic kidney diseases. In this randomized, controlled, prospective, parallel open study 70 patients were treated for 24 weeks with either reference β recombinant erythropoietin (100 IU/kg) or biosimilar β recombinant erythropoietin (100 IU/kg). The primary efficacy endpoint was the hemoglobin and hematocrit levels from baseline to 24 week of treatment. The secondary endpoints were safety, weekly doses of both erythropoietins required to maintain hemoglobin levels and immunogenicity. There was no significant difference between the two preparations in terms of hemoglobin and hematocrit levels achieved. The weekly doses of both erythropoietins required to maintain hemoglobin levels were the same in both groups. The frequency of adverse events was similar in the two groups of treatment. Two patients of the reference erythropoietin group developed anti-erythropoietin antibodies. The biosimilar erythropoietin was comparable since the safety and efficacy point of view with the innovator erythropoietin in hemodialysis patients based on hemoglobin changes. The biosimilar erythropoietin when administered subcutaneously will be equally efficacious and may be interchangeable as therapy.
Maria del Carmen Popoca-Martínez,
Raúl Meixueiro-Montes De Oca,
Comparison of the Therapeutic Effects of Two Recombinant Erythropoietin Beta, Biosimilar and Reference Formulations in Patients with Chronic Kidney Disease under Hemodialysis, Clinical Medicine Research.
Vol. 3, No. 5,
2014, pp. 136-141.
Brockmöller J, Köchling J, Weber W, et al. The pharmacokinetics and pharmacodynamics of recombinant human erythropoietin in haemodialysis patients. Br J Clin Pharmac 1992; 34: 499-508.
Hsu CY, McCulloch CE, Curhan GC. Epidemiology of anemia associated with chronic renal insufficiency among adults in the United States: results from the Third National Health and Nutrition Examination Survey. J Am Soc Nephrol 2002; 13: 504-510.
McClellan W, Aronoff SL, Bolton WK, et al. The prevalence of anemia in patients with chronic kidney disease. Curr Med Res Opin 2004; 20: 1501-1510.
Besarab A, Bolton WK, Browne JK, 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; 339: 584-590.
Revicki Da, Brown RE, Feeney DH, et al. Health-related quality of life associated with recombinant human erythropoietin therapy for predialysis chronic renal disease patients. Am J Kidney Dis 1995; 25: 548-554.
Collins AJ, Brenner RM, Ofman JJ; et al. Epoetin alfa use in patients with ESRD : an analysis of recent US prescribing patterns and hemoglobin outcomes. Am J Kidney Dis 2005; 46: 481-488.
Mayer G, Thum J, Cada EM, et al. Working capacity is increased following recombinant human erythropoietin treatment. Kidney Int 1988; 34: 525-528.
Macdougall IC, Lewis NP, Saunders MJ, et al. Long-term cardiorespiratory effects of amelioration of renal anemia by erythropoietin. Lancet 1990: 335: 489-493.
Delano BG. Improvements in quality of life following treatment with r-HuEPO in anemia hemodialysis patients. Am J Kidney Dis 1989; 14: 14-18.
Evans RW, Rader B, Mannien DL, Cooperative Multicenter EPO Clinical Trial Group. The quality of life of hemodialysis recipients treated with recombinant human erythropoietin. JAMA 1990; 263: 825-830.
Ifudu O. Patient characteristics determining rHuEPO dose requirements. Nephrol Dial Transplant 2002; 17(5): 38-41.
Stenvinkel P, Barany P. Anemia, rHuEPO resistance, and cardiovascular disease in end-stage renal failure: links to inflammation and oxidative stress. Nephrol Dial Transplant 2002; 17(5): 32-37.
Zeid RJ. Regulatory and development issues in the demonstration of therapeutic equivalence for multisource biotechderivated pharmaceuticals. Drug Information Journal 2000; 34: 919-959.
Schellekens H, Ryff JC. Biogenerics: the off-patient biotech products. Trends Pharmacol Sci 2002; 23: 119-121.
Loughnan A, Ali GR, Abeygunasekara SC. Comparison of the therapeutic efficacy of epoetin beta and epoetin alfa in maintenance phase hemodialysis patients. REn Fail 2011: 33(3): 373-375.
Storring PL, Tiplady RJ, Gaintes Das RE, et la. Epoetin alfa ans beta differ in their erythropoietin isoform compositions and biological properties. Br J Haematol 1998; 100: 79-89.
Chamberlain P. Biogenerics: Europe takes another step forward while the FDA dives for cover. Drug Discov Today 2004; 9: 817-820.
Hernandez-Bastida A, Meixueiro-Montes de Oca R. Equivalence on efficay and safety of two formulations of insulin glargine (biosimilar and reference) in the treatment of patients with type 2 diabetes. Clinical Medicine Research 2014; 3(2): 50-55.
Palma-Aguirre J, Alvarez-Etchegaray S, Meixueiro-Montes de Oca R. Pharmacokinetic and pharmacodynamic biocomparability of two r-hGH (innovator and biosimilar) formulations after subcutaneous administration in healthy volunteers. Int J Pharm Pract & Drug Res 2014; 4(1): 62-66.
Locatelli F, Aljama P, Barany P, et al. Revised European best practice guidelines for the management of anemia in patients with chronic renal failure. Nephrol Dial Transplant 2004; 19(Suppl 2): 1-47.
Furuland H, Linde T, Ahlmen J, et al. A randomised controlled trial of haemoglobin normalisation with epoetin alfa in pre-dyalisis and dialysis patients. Nephrol Dial Transplant 2003; 18(2): 353-361.
Ebben JP, Gilbertson DT, Foley RN, Collins AJ. Hemoglobin level variability: associations with comorbidity, intercurrent events and hospitalizations. Clin J Am Soc Nephrol 2006; 1(6): 1205-1210.
Berns JS, Elzein H, Lynn RI, et al. Hemoglobin variability in epoetin-treated hemodialysis patients. Kidney Int 2003; 64(4): 1514-1521.
Breiterman-White R. Hemoglobin variability: management inevitable changes in clinical status. Nephrol Nurs J 2005; 32: 549-552.
Fishbane S, Berns JS. Hemoglobin cycling in hemodialysis patients treated with recombinant human erythropoietin- Kidney Int 2005; 68(3): 1337-1343.
Fishbane S, Berns JS,. Evidence and implications of hemoglobin cycling in anemia management. Nephrol Dial Transplant 2007; 22(8): 2129-2132.
Jacquot C, Ferragu-Haguet M, Lefebvre A, et al. Recombinant erythropoietin and blood pressure. Lancet 1987; 2: 1083-1085.
Klinkmann H, Wieczorek L, Scigalla P. Adverse events of subcutaneous recombinant human erythropoietin therapy: results of a controlled multicenter European study. Artif Organs 1993; 17: 219-225.