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BMC Nephrology Mar 2011Anemia is common among peritoneal dialysis (PD) patients, and most patients require erythropoiesis-stimulating agents (ESA) to maintain their hemoglobin concentrations...
BACKGROUND
Anemia is common among peritoneal dialysis (PD) patients, and most patients require erythropoiesis-stimulating agents (ESA) to maintain their hemoglobin concentrations within current guideline recommendations. Darbepoetin alfa is an ESA with a 3-fold longer half-life and greater in vivo biological activity than recombinant human erythropoietin, allowing less frequent dosing that may simplify anemia management in these patients, providing benefits to patients, care givers and health care providers. Clinical studies have confirmed the efficacy and safety of darbepoetin alfa administered at extended dosing intervals. However, there are limited data on the management of anemia with ESAs in PD patients in routine clinical practice. The aim of this multicenter observational study in European and Australian dialysis patients was to evaluate darbepoetin alfa administered once every 2 weeks (Q2W) in routine clinical practice for 12 months.
METHODS
PD patients ≥18 years old and converting to treatment with darbepoetin alfa Q2W were eligible for enrollment regardless of previous or current ESA use. Patients enrolled in the study were treated according to local usual clinical practice. Data were collected up to 6 months prior to and 12 months after conversion to darbepoetin alfa Q2W. The primary endpoint was hemoglobin concentration 12 months after conversion to darbepoetin alfa Q2W.
RESULTS
Of the 741 eligible PD patients (mean age, 61 years; male, 57%), 640 (86%) completed the study. Mean hemoglobin concentration (g/dL) was 11.69 (95% CI, 11.53-11.86) 6 months before the conversion, 12.25 (95% CI, 12.13-12.38) at conversion, and 11.88 (95% CI, 11.74-12.02) 12 months after conversion to darbepoetin alfa Q2W. The weekly equivalent ESA dose (μg/wk) was a geometric mean of 25.24 (95% CI, 23.46-27.15) 6 months before conversion, 20.90 (95% CI, 19.13-22.83) immediately before conversion, 18.89 (95% CI, 18.13-19.68) at conversion and 19.04 (95% CI, 17.69-20.49) 12 months after conversion. Twelve months after conversion, 70% of patients were receiving darbepoetin alfa Q2W and 73% had hemoglobin concentrations >11.0 g/dL.
CONCLUSION
In this large observational study, PD patients were able to maintain mean hemoglobin concentrations >11.0 g/dL after conversion to extended dosing of darbepoetin alfa Q2W, with no mean dose increase.
Topics: Anemia; Darbepoetin alfa; Erythrocyte Indices; Erythropoietin; Female; Hematinics; Humans; Male; Observation; Peritoneal Dialysis
PubMed: 21435267
DOI: 10.1186/1471-2369-12-13 -
Journal of the American Society of... Nov 2020
Topics: Anemia; Darbepoetin alfa; Double-Blind Method; Glycine; Humans; Isoquinolines; Japan; Renal Dialysis; Renal Insufficiency, Chronic
PubMed: 32915765
DOI: 10.1681/ASN.2020071096 -
European Journal of Clinical... Apr 2010Cloning of the human erythropoietin (EPO) gene and development of the first recombinant human erythropoietin (rHuEPO) drug were truly breakthroughs. This allowed a... (Review)
Review
Discovery and basic pharmacology of erythropoiesis-stimulating agents (ESAs), including the hyperglycosylated ESA, darbepoetin alfa: an update of the rationale and clinical impact.
Cloning of the human erythropoietin (EPO) gene and development of the first recombinant human erythropoietin (rHuEPO) drug were truly breakthroughs. This allowed a deeper understanding of the structure and pharmacology of rHuEpo, which in turn inspired the discovery and development of additional erythropoiesis-stimulating agents (ESAs). In vivo specific activity and serum half-life of rHuEPO are influenced by the amount and structure of the attached carbohydrate. Increased numbers of sialic acids on carbohydrate attached to rHuEPO correlated with a relative increase in in-vivo-specific activity and increased serum half-life. The effect of increasing the number of sialic-acid-containing carbohydrates on in-vivo-specific activity was explored. Initial research focused on solving the problem of how the protein backbone could be engineered so a cell would add more carbohydrate to it. Additional work resulted in darbepoetin alfa, a longer-acting molecule with two additional carbohydrate chains.
Topics: Carbohydrates; Darbepoetin alfa; Erythropoietin; Half-Life; Hematinics; Humans; N-Acetylneuraminic Acid; Protein Binding; Recombinant Proteins
PubMed: 20127232
DOI: 10.1007/s00228-009-0780-y -
American Journal of Nephrology 2004This multicenter, open-label study determined safety and efficacy of once-every-other-week administration of darbepoetin alfa for anemia of chronic kidney disease in... (Clinical Trial)
Clinical Trial
AIM
This multicenter, open-label study determined safety and efficacy of once-every-other-week administration of darbepoetin alfa for anemia of chronic kidney disease in erythropoietin-naive patients not on dialysis.
METHODS
Participants with hemoglobin levels <11.0 g/dl at baseline were administered darbepoetin alfa at an initial dosage of 0.75 microg/kg once every other week. The dose was titrated to achieve and maintain a hemoglobin response, defined as a hemoglobin range of between 11.0 and 13.0 g/dl for up to 24 weeks. The primary end point was the dose of darbepoetin alfa at initial hemoglobin response.
RESULTS
Six hundred and eight patients were enrolled, and 463 completed the study; 95% (95% confidence interval: 0.93, 0.97) of the patients who completed treatment achieved a hemoglobin response. The mean darbepoetin alfa dose at the time of response was 63.5 +/- (SD) 16.9 microg, and the mean time to hemoglobin response was 5.7 +/- (SD) 4.5 weeks. Oral iron therapy was administered to 60% and intravenous iron to 16% of the participants. Darbepoetin alfa was well tolerated, and adverse events were consistent with those expected in patients with chronic kidney disease.
CONCLUSION
Darbepoetin alfa administered once every other week is effective and safe for achieving and maintaining target hemoglobin levels in anemic patients with chronic kidney disease.
Topics: Adult; Aged; Aged, 80 and over; Anemia; Darbepoetin alfa; Drug Therapy, Combination; Erythropoietin; Female; Hemoglobins; Humans; Iron; Kidney Failure, Chronic; Male; Middle Aged; Treatment Outcome
PubMed: 15331889
DOI: 10.1159/000080452 -
BioDrugs : Clinical Immunotherapeutics,... Feb 2020Darbepoetin-alfa is an erythropoiesis-stimulating agent (ESA) with a long elimination half-life that achieves better hemoglobin (Hb) stability than short-acting ESAs. (Randomized Controlled Trial)
Randomized Controlled Trial
Efficacy and Safety of CKD-11101 (Proposed Biosimilar of Darbepoetin-Alfa) Compared with Darbepoetin-Alfa in Patients on Hemodialysis: A Randomized, Double-Blinded, Parallel-Group Phase III Study.
BACKGROUND
Darbepoetin-alfa is an erythropoiesis-stimulating agent (ESA) with a long elimination half-life that achieves better hemoglobin (Hb) stability than short-acting ESAs.
OBJECTIVE
We aimed to evaluate the efficacy and safety of intravenous CKD-11101 (a biosimilar of darbepoetin-alfa) compared with those of darbepoetin-alfa in hemodialysis patients.
METHODS
The study was performed in 24 centers in Korea between June 2015 and June 2017. The study subjects were randomized in a double-blind manner. The follow-up duration was 24 weeks, which consisted of 20 weeks of maintenance and 4 weeks of evaluation period. All patients underwent a stabilization period to achieve a target baseline Hb of 10-12 g/dL before randomization. Following randomization, patients received darbepoetin-alfa or CKD-11101 weekly or biweekly.
RESULTS
A total of 403 patients were randomized into two groups, and a total of 325 patients (80.6%) completed the investigation. The differences between the two groups in terms of change in the average Hb level from baseline to evaluation were not significant. The average administered dose of ESA was similar between the groups. There was no difference in the proportion of patients who maintained the target Hb during the evaluation period [60.4% vs. 66.2% in the CKD-11101 and darbepoetin-alfa groups, respectively (p = 0.3038)]. In addition, the safety analysis, consisting of adverse events and adverse drug reactions, showed comparable results between the two groups.
CONCLUSION
The changes in the level of Hb, dose of erythropoietin, and achievement rate of the target Hb during the study period were comparable between the groups. CKD-11101 has an equivalent efficacy and safety compared with darbepoetin-alfa in patients undergoing hemodialysis.
Topics: Adult; Biosimilar Pharmaceuticals; Darbepoetin alfa; Double-Blind Method; Drug-Related Side Effects and Adverse Reactions; Epoetin Alfa; Female; Hemoglobins; Humans; Male; Middle Aged; Renal Dialysis; Renal Insufficiency, Chronic
PubMed: 31749113
DOI: 10.1007/s40259-019-00396-9 -
Clinical and Experimental Nephrology Feb 2021Hyporesponsiveness to erythropoiesis-stimulating agents (ESAs) is associated with cardiovascular events and poor renal outcome in patients with chronic kidney disease...
BACKGROUND
Hyporesponsiveness to erythropoiesis-stimulating agents (ESAs) is associated with cardiovascular events and poor renal outcome in patients with chronic kidney disease (CKD). This study aimed to investigate the initial responsiveness to darbepoetin alfa (DA) and its contributing factors using the data from the BRIGHTEN.
METHODS
Of 1980 patients enrolled at 168 facilities, 1695 were included in this analysis [285 patients were excluded mainly due to lack of hemoglobin (Hb) values]. The initial ESA response index (iEResI) was defined as a ratio of Hb changes over 12 weeks after DA administration per weight-adjusted total DA dose and contributing factors to iEResI were analyzed.
RESULTS
The mean age was 70 ± 12 years (male 58.8%; diabetic nephropathy 27.6%). The median creatinine and mean Hb levels at DA initiation were 2.62 mg/dL and 9.8 g/dL, respectively. The most frequent number of DA administration during 12 weeks was 3 times (41.1%), followed by 4 (15.6%) times with a wide distribution of the total DA dose (15-900 μg). Remarkably, 225 patients (13.3%) did not respond to DA. Multivariate analysis showed that male gender, hypoglycemic agent use, iron supplementation, high eGFR, low Hb, low CRP, low NT-proBNP, and low urinary protein-creatinine ratio were independently associated with better initial response to DA (P = < 0.0001, 0.0108, < 0.0001, 0.0476, < 0.0001, 0.0004, 0.0435, and 0.0009, respectively).
CONCLUSIONS
Non-responder to DA accounted for 13.3% of patients with non-dialysis CKD. Iron supplementation, low CRP, low NT-proBNP, and less proteinuria were predictive and modifiable factors associated with better initial response to DA.
Topics: Aged; Aged, 80 and over; Anemia; Cardiovascular Diseases; Darbepoetin alfa; Female; Humans; Male; Middle Aged; Renal Dialysis; Renal Insufficiency, Chronic
PubMed: 32949295
DOI: 10.1007/s10157-020-01969-7 -
Nephrology, Dialysis, Transplantation :... May 2004Darbepoetin alfa is a unique molecule that stimulates erythropoiesis by the same mechanism as endogenous erythropoietin. Due to its approximately 3-fold longer half-life... (Clinical Trial)
Clinical Trial Comparative Study
Darbepoetin alfa effectively maintains haemoglobin concentrations at extended dose intervals relative to intravenous or subcutaneous recombinant human erythropoietin in dialysis patients.
BACKGROUND
Darbepoetin alfa is a unique molecule that stimulates erythropoiesis by the same mechanism as endogenous erythropoietin. Due to its approximately 3-fold longer half-life and greater biological activity than recombinant human erythropoietin (rHuEpo), darbepoetin alfa maintains effective haemoglobin control at extended dose intervals compared with rHuEpo. This study assessed the efficacy and safety of unit doses of darbepoetin alfa for the treatment of renal anaemia.
METHODS
In this multicentre, prospective, open-label study, 1502 dialysis subjects maintained on stable rHuEpo treatment were switched to darbepoetin alfa at extended dose intervals by the same route of administration as previous rHuEpo therapy [intravenous (i.v.), n = 900 or subcutaneous (s.c.), n = 602]. Subjects receiving rHuEpo two (n = 408, 27%) or three times (n = 884, 59%) a week were switched to darbepoetin alfa once a week, and those receiving rHuEpo once a week (n = 210, 14%) were switched to darbepoetin alfa once every 2 weeks. The unit doses of darbepoetin alfa (10-150 microg) were titrated to maintain haemoglobin concentrations of 10-13 g/dl for 24 weeks.
RESULTS
Haemoglobin concentrations were maintained effectively in subjects regardless of whether they received darbepoetin alfa once a week or once every 2 weeks. The overall mean change in haemoglobin from baseline to the evaluation period (weeks 21-24) was +0.10 g/dl [95% confidence interval (CI) 0.04+/- 0.17]. The mean haemoglobin concentration increased by 0.19 g/dl (95% CI 0.11+/-0.27) in subjects receiving i.v. darbepoetin alfa, and was unchanged (-0.02 g/dl; 95% CI -0.12 to 0.07) in patients treated with s.c. darbepoetin alfa. Subjects with baseline haemoglobin < 11 g/dl experienced a clinically relevant increase in mean haemoglobin concentration of 0.67 g/dl (95% CI 0.56+/-0.77) from baseline to the evaluation period. The mean weekly i.v. and s.c. darbepoetin alfa dosage requirements during the evaluation period were 19.9 microg/week (95% CI 19.02+/-20.87) and 21.6 microg/week (95% CI 20.36+/- 22.94), respectively. Darbepoetin alfa was well tolerated and the safety profile was consistent with previous trials with darbepoetin alfa in dialysis subjects.
CONCLUSIONS
Treating renal anaemia with darbepoetin alfa administered at extended dose intervals is both effective and well tolerated. Moreover, administration of darbepoetin alfa by both the i.v. and s.c. route is associated with stable haemoglobin concentrations.
Topics: Adult; Aged; Anemia; Darbepoetin alfa; Erythropoietin; Female; Hemoglobins; Humans; Injections, Intravenous; Injections, Subcutaneous; Male; Middle Aged; Racial Groups; Recombinant Proteins; Renal Dialysis
PubMed: 14993489
DOI: 10.1093/ndt/gfh106 -
American Journal of Kidney Diseases :... Jun 2003
Comparative Study
Topics: Darbepoetin alfa; Dose-Response Relationship, Drug; Drug Costs; Epoetin Alfa; Erythropoietin; Humans; Injections, Intravenous; Injections, Subcutaneous; Randomized Controlled Trials as Topic; Recombinant Proteins
PubMed: 12776288
DOI: 10.1016/s0272-6386(03)00511-0 -
Clinics in Perinatology Sep 2015Erythropoiesis-stimulating agents (ESAs) such as erythropoietin have been studied as red cell growth factors in preterm and term infants for more than 20 years. Recent... (Review)
Review
Erythropoiesis-stimulating agents (ESAs) such as erythropoietin have been studied as red cell growth factors in preterm and term infants for more than 20 years. Recent studies have evaluated darbepoetin (Darbe, a long-acting ESA) for both erythropoietic effects and potential neuroprotection. We review clinical trials of Darbe in term and preterm infants, which have reported significant erythropoietic uses and neuroprotective effects. ESAs show great promise in decreasing or eliminating transfusions, and in preventing and treating brain injury in term and preterm infants.
Topics: Darbepoetin alfa; Drug Administration Schedule; Hematinics; Humans; Infant, Newborn; Infant, Premature; Infant, Premature, Diseases; Neuroprotection; Treatment Outcome
PubMed: 26250917
DOI: 10.1016/j.clp.2015.04.016 -
Current Drug Safety 2022Anemia is one of the most common complications of Chronic Kidney Disease (CKD). The vast majority of Egyptian CKD patients are interchangeably treated with Darbepoetin... (Comparative Study)
Comparative Study Randomized Controlled Trial
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.
Topics: Anemia; Darbepoetin alfa; Egypt; Epoetin Alfa; Erythropoietin; Hemoglobins; Humans; Kidney Failure, Chronic; Prospective Studies; Recombinant Proteins; Renal Dialysis; Renal Insufficiency, Chronic
PubMed: 34814819
DOI: 10.2174/1568009621666211123095129