Cohort Prospective Study to Evaluate Immunogenicity of Epodion® (Biosimilar Epoetin-α) in Anemia Associated with Chronic Kidney Disease (CKD) Patients
Methods: This prospective, open label, single arm, and multicenter study enrolled patients with anemia associated with CKD under hemodialysis treatment. Patient eligibility was assessed within the 4-week screening period. Blood samples for determination of erythropoietin antibody (Anti-Drug Antibody) were taken at week-0, 24, and 52 using a validated and highly sensitive bridging ELISA method. Evaluation of Neutralizing Antibody (NAb) was carried out to confirm the impact of the antibody to pharmacological activity (e.g., antibody-mediated PRCA) when the ADA detection of patients was positive after screening and confirmatory assay. Results: Results from all tested patients show that Epodion could maintain hemoglobin and hematocrit levels. ADA detection using ELISA assay yielded negative results for all plasma samples of week-24 and week-52, so the evaluation of NAb was not carried out. No adverse events were considered relevant to tested product. Conclusion: This study proves no immunogenic effect of Epodion on stimulating immune system’s antibodies in Indonesian patients with CKD-associated anemia.
Kidney Disease: Improving Global Outcomes (KDIGO) CKD Work Group. KDIGO 2012 clinical practice guideline for the evaluation and management of chronic kidney disease. Kidney Int Suppl. 2013;3:1–150.
Kementerian Kesehatan RI. Situasi penyakit ginjal kronis. Jakarta: Pusat Data dan Informasi Kementrian Kesehatan RI; 2017.
Luyckx VA, Tonelli M, Stanifer JW. The global burden of kidney disease and the sustainable development goals. Bull World Health Organ. 2018;96(6):414-22.
Indonesian Ministry of Health. Basic health research report (In Bahasa: Riset Kesehatan Dasar). Jakarta; 2013.
Kalantar-Zadeh K. History of erythropoiesis-stimulating agents, the development of biosimilars, and the future of anemia treatment in nephrology. Am J Nephrol. 2017;45(3):235–47.
European Medicines Agency (EMA). Biosimilars in the EU: information guide for healthcare professionals. European Medicines Agency; 2017.
World Health Organization (WHO). Guidelines On evaluation of similar biotherapeutic products (SBPs). Geneva; 2009.
Food and Drug Administration (FDA). Immunogenicity testing of therapeutic protein products - developing and validating assays for anti-drug antibody detection. 2019.
Chow, SC. Biosimilars: design and analysis of follow-on biologics. CRC Press; 2013.
Krishna M, Nadler SG. Immunogenicity to biotherapeutics - The role of anti-drug immune complexes. Front Immunol. 2016;7(Feb).
Chirmule N, Jawa V, Meibohm B. Immunogenicity to therapeutic proteins: Impact on PK/PD and efficacy. AAPS J. 2012;14(2):296–302.
Grams ME, Yang W, Rebholz CM, et al. Risks of adverse events in advanced CKD: the chronic renal insufficiency cohort (CRIC) study. Am J Kidney Dis. 2017;70(3):337-46.
Hörl WH, Locatelli F, Haag-Weber M, Ode M, Roth K. Prospective multicenter study of HX575 (biosimilar epoetin-α) in patients with chronic kidney disease applying a target hemoglobin of 10 - 12 g/dl. Clin Nephrol. 2012;78(1):24–32.
London G, Mann J, Goldsmith D, et al. Long-term treatment with biosimilar epoetin-α (HX575) in hemodialysis patients with renal anemia: Real-world effectiveness and safety in the MONITOR-CKD5 study. Clin Nephrol. 2018;89(1):1–9.
Hustrini NM, Siregar P, Setiawati A, Nugroho P. Clinical comparison of Renogen, a biosimilar Epoetin-a, with the originator, eprex, in chronic kidney disease anemia in Indonesia: A preliminary study. Acta Med Indones. 2019;51(3):230–7.
Haag-Weber M, Eckardt KU, Hörl WH, Roger SD, Vetter A, Roth K. Safety, immunogenicity and efficacy of subcutaneous biosimilar epoetin-α (HX575) in non-dialysis patients with renal anemia: A multi-center, randomized, double-blind study. Clin Nephrol. 2012;77(1):8–17.
Casadevall N. Antibodies against rHuEPO: Native and recombinant. Nephrol Dial Transplant. 2002;17(Suppl. 5):42–7.
Shin SK, Moon SJ, Ha SK, et al. Immunogenicity of recombinant human erythropoietin in Korea: A two-year cross-sectional study. Biologicals [Internet]. 2012;40(4):254–61. Available from: http://dx.doi.org/10.1016/j.biologicals.2012.02.003
Phrommintikul A, Haas SJ, Elsik M, Krum H. Mortality and target haemoglobin concentrations in anaemic patients with chronic kidney disease treated with erythropoietin: a meta-analysis. Lancet. 2007;369(9559):381-8.
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