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The Journal of the Association of... Jan 2019
Randomized Controlled Trial
Darbepoetin Alfa Versus Erythropoietin Alfa for Treatment of Renal Anemia in Patients with Chronic Kidney Disease at the Pre-Dialysis Stage: A Randomized Non-inferiority Trial.
Topics: Anemia; Darbepoetin alfa; Erythropoietin; Hematinics; Hemoglobins; Humans; Kidney Failure, Chronic; Recombinant Proteins; Renal Dialysis; Renal Insufficiency, Chronic
PubMed: 30935177
DOI: No ID Found -
American Journal of Hematology Sep 2010This study evaluated efficacy and safety of darbepoetin alfa administered every 3 weeks (Q3W) at fixed doses of 300 or 500 μg with or without intravenous (IV) iron in... (Randomized Controlled Trial)
Randomized Controlled Trial
This study evaluated efficacy and safety of darbepoetin alfa administered every 3 weeks (Q3W) at fixed doses of 300 or 500 μg with or without intravenous (IV) iron in treating anemia in patients receiving multicycle chemotherapy. This Phase 2, double-blind, 2 × 2 factorial study randomized patients to one of four treatment arms; darbepoetin alfa 300 μg (n = 62), darbepoetin alfa 300 μg plus IV iron (n = 60), darbepoetin alfa 500 μg (n = 60), or darbepoetin alfa 500 μg plus IV iron (n = 60). Patients had nonmyeloid malignancies, hemoglobin levels ≤10 g dL(-1), and no iron deficiency. Primary endpoint was achievement of target hemoglobin (≥11 g dL(-1)). Secondary endpoints included incidence of transfusions and change in Functional Assessment of Cancer Therapy Fatigue (FACT-F) score from baseline to end of study. Safety was evaluated by incidence of adverse events. No evidence of a statistically significant interaction between darbepoetin alfa dose received and IV iron usage was observed, therefore, results are provided separately comparing darbepoetin alfa doses and comparing IV iron usage groups. Similar proportions of patients receiving darbepoetin alfa 300 or 500 μg achieved target hemoglobin (75 and 78%, respectively); Kaplan-Meier median time to target hemoglobin was 10 and 8 weeks, respectively. More patients receiving IV iron (82%) than not receiving IV iron (72%) achieved hemoglobin target. Adverse events profiles were similar for darbepoetin alfa treatment groups. Transient anaphylactoid reactions were reported in two patients receiving IV iron. Darbepoetin alfa at 300 μg Q3W and 500 μg Q3W showed similar benefit, while added IV iron improved treatment response in these patients.
Topics: Aged; Anemia; Darbepoetin alfa; Double-Blind Method; Erythropoietin; Female; Hemoglobins; Humans; Infusions, Intravenous; Iron; Male; Middle Aged; Neoplasms; Time Factors
PubMed: 20661916
DOI: 10.1002/ajh.21779 -
The Cochrane Database of Systematic... Mar 2014Erythropoiesis-stimulating agents are used to treat anaemia in people with chronic kidney disease (CKD). Several agents are available including epoetin alfa or beta as... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Erythropoiesis-stimulating agents are used to treat anaemia in people with chronic kidney disease (CKD). Several agents are available including epoetin alfa or beta as well as agents with a longer duration of action, darbepoetin alfa and methoxy polyethylene glycol-epoetin beta.
OBJECTIVES
To assess the benefits and harms of darbepoetin alfa to treat anaemia in adults and children with CKD (stages 3 to 5, 5D, and kidney transplant recipients).
SEARCH METHODS
We searched the Cochrane Renal Group's Specialised Register (to 13 January 2014) through contact with the Trials' Search Co-ordinator using search terms relevant to this review. Studies contained in the Specialised Register are identified through search strategies specifically designed for CENTRAL, MEDLINE and EMBASE.
SELECTION CRITERIA
We included randomised controlled trials of any darbepoetin alfa treatment of at least three months duration in adults or children with CKD (any stage).
DATA COLLECTION AND ANALYSIS
Data were extracted by two independent investigators. Patient-centred outcomes (need for blood transfusion, iron therapy, progression of kidney disease, total and cardiovascular mortality, cardiovascular events, cancer, hypertension, seizures, and health-related quality of life) and other outcomes (haemoglobin levels) were assessed using random effects meta-analysis. We calculated risk ratios for dichotomous outcomes and mean differences for continuous outcomes, both with 95% confidence intervals.
MAIN RESULTS
We identified 32 studies comprising 9414 participants; 21 studies in 8328 participants could be included in our meta-analyses. One study (4038 participants) compared darbepoetin alfa to placebo, 16 studies (2955 participants) compared darbepoetin alfa to epoetin alfa or beta, four studies (1198 participants) compared darbepoetin alfa to methoxy polyethylene glycol-epoetin beta, three studies (420 participants) compared more frequent with less frequent darbepoetin alfa administration and four studies (303 participants) compared intravenous with subcutaneous darbepoetin alfa administration.In a single large study, darbepoetin alfa reduced the need for blood transfusion and iron therapy compared with placebo in adults with CKD stage 3 to 5, but had little or no effect on survival, increased risks of hypertension, and had uncertain effects on quality of life. Data comparing darbepoetin alfa with epoetin alfa or beta or methoxy polyethylene glycol-epoetin beta were sparse and inconclusive. Comparisons of differing dosing schedules and routes of administration were compared in small numbers of participants and studies. Evidence for treatment effects of darbepoetin alfa were particularly limited for children with CKD, adults with CKD stage 5D, and recipients of a kidney transplant.Studies included in this review were generally at high or unclear risk of bias for all items (random sequence generation, allocation concealment, incomplete outcome data, blinding of participants and personnel, blinding of outcome assessment, selective outcome reporting, intention to treat analysis and other sources of bias). One large study comparing darbepoetin alfa with placebo was at low risk of bias for most items assessed.
AUTHORS' CONCLUSIONS
Data suggest that darbepoetin alfa effectively reduces need for blood transfusions in adults with CKD stage 3 to 5, but has little or no effect on mortality or quality of life. The effects of darbepoetin alfa in adults with CKD stage 5D and kidney transplant recipients and children with CKD remain uncertain as do the relative benefits and harms of darbepoetin alfa compared with other ESAs (epoetin alfa or beta and methoxy polyethylene glycol-epoetin beta).
Topics: Adult; Anemia; Child; Darbepoetin alfa; Epoetin Alfa; Erythropoietin; Hematinics; Humans; Kidney Transplantation; Polyethylene Glycols; Randomized Controlled Trials as Topic; Recombinant Proteins; Renal Insufficiency, Chronic
PubMed: 24683046
DOI: 10.1002/14651858.CD009297.pub2 -
Journal of Clinical Oncology : Official... May 2006
Topics: Anemia; Antineoplastic Agents; Clinical Trials as Topic; Darbepoetin alfa; Dose-Response Relationship, Drug; Epoetin Alfa; Erythropoietin; Hematinics; Humans; Neoplasms; Recombinant Proteins; Therapeutic Equivalency
PubMed: 16710021
DOI: 10.1200/JCO.2006.05.7794 -
Therapeutic Apheresis and Dialysis :... Apr 2020The aim of this study was to compare the efficacy and safety of intravenous JR-131, a darbepoetin alfa biosimilar, to darbepoetin alfa in hemodialysis patients with... (Comparative Study)
Comparative Study Randomized Controlled Trial
The aim of this study was to compare the efficacy and safety of intravenous JR-131, a darbepoetin alfa biosimilar, to darbepoetin alfa in hemodialysis patients with renal anemia. In this 24-week, multicenter, randomized, double-blinded, parallel-group phase 3 study, 334 hemodialysis patients with renal anemia who had been receiving darbepoetin alfa were randomized to either JR-131 or darbepoetin alfa group. The initial dose was set based on the darbepoetin alfa dose during the observation period. The primary endpoint was change in hemoglobin level from baseline to end of treatment. The 95% confidence interval of the difference in the change in hemoglobin level between the groups was -0.19 to -0.20 g/dL, within the equivalent margin of -0.5 to 0.5 g/dL. No notable treatment-emergent adverse events were observed in either group. JR-131 was therapeutically equivalent to darbepoetin alfa, and the safety profile of JR-131 was similar to that of darbepoetin alfa.
Topics: Adult; Aged; Aged, 80 and over; Anemia; Biosimilar Pharmaceuticals; Darbepoetin alfa; Double-Blind Method; Female; Hematinics; Humans; Male; Middle Aged; Renal Dialysis; Renal Insufficiency, Chronic
PubMed: 31325212
DOI: 10.1111/1744-9987.13422 -
Pediatric Nephrology (Berlin, Germany) Aug 2006Darbepoetin alfa, an erythropoiesis-stimulating glycoprotein, has proved efficacious in the treatment of anemia of chronic kidney disease (CKD) in adult subjects.... (Randomized Controlled Trial)
Randomized Controlled Trial
Darbepoetin alfa, an erythropoiesis-stimulating glycoprotein, has proved efficacious in the treatment of anemia of chronic kidney disease (CKD) in adult subjects. However, little information is available from pediatric populations. We conducted an open-label, non-inferiority, 28-week study comparing the efficacy of darbepoetin alfa with that of recombinant human erythropoietin (rHuEpo) in pediatric subjects with CKD. Subjects, aged 1-18, who were receiving stable rHuEpo treatment (n=124) were randomized (1:2) to either continue receiving rHuEpo or convert to darbepoetin alfa, with doses titrated to achieve and maintain hemoglobin (Hb) levels between 10.0 and 12.5 g/dl. Darbepoetin alfa was considered to be non-inferior to rHuEpo if the lower limit of the two-sided 95% confidence interval (CI) for the difference in the mean change in Hb between the two treatment groups was above -1.0 g/dl. The adjusted mean change in Hb between the baseline and the evaluation period for the rHuEpo and darbepoetin alfa groups was -0.16 g/dl and 0.15 g/dl, respectively, with a difference of 0.31 g/dl (95% CI: -0.45, 1.07) between the means. These results, and the comparable safety profiles, demonstrate that darbepoetin alfa is non-inferior to rHuEpo in the treatment of anemia in pediatric patients with CKD.
Topics: Anemia; Child; Chronic Disease; Darbepoetin alfa; Erythropoietin; Female; Hematinics; Humans; Kidney Diseases; Male
PubMed: 16724235
DOI: 10.1007/s00467-006-0071-0 -
Oncology (Williston Park, N.Y.) Sep 2002Barriers to use of erythropoietic therapy in cancer patients include nonresponse in a sizable proportion, resultant lowering of cost-effectiveness, and inconvenience.... (Review)
Review
Barriers to use of erythropoietic therapy in cancer patients include nonresponse in a sizable proportion, resultant lowering of cost-effectiveness, and inconvenience. Darbepoetin alfa represents the outcome of efforts to develop agents with improved erythropoietic potency. This agent has been shown to produce high dose-related response rates, reduce risk of transfusion, and produce dose-related rapidity of response in cancer patients; no loss in dose-efficiency is observed with once-every-2-week dosing compared with weekly dosing, and the feasibility of every-3-week dosing has been demonstrated. In addition, the characteristics of this agent may permit a treatment schedule consisting of front loading with an optimal dose followed by low-dose maintenance, which may further improve dose-efficiency and cost-effectiveness of treatment. The characteristics of darbepoetin alfa suggest the ability to improve overall quality of erythropoietic therapy, which may increase its utilization in patients who would benefit from such treatment.
Topics: Anemia; Antineoplastic Agents; Clinical Trials as Topic; Darbepoetin alfa; Drug Administration Schedule; Erythropoietin; Hemoglobins; Humans; Neoplasms; Recombinant Proteins
PubMed: 12380957
DOI: No ID Found -
The Journal of Veterinary Medical... Apr 2021Iron metabolism, hepcidin and some blood profiles were investigated in 13 healthy and 31 chronic kidney disease (CKD) dogs. The study consisted of 2 experiments,...
Iron metabolism, hepcidin and some blood profiles were investigated in 13 healthy and 31 chronic kidney disease (CKD) dogs. The study consisted of 2 experiments, experiment I included healthy dogs (CONT) and CKD dogs (stage 2, 3 and 4), while experiment II consisted of anemic CKD dogs subjected to 28-day darbepoetin alfa treatment. The response to darbepoetin alfa could divide anemic CKD dogs into responder (RP) and non-responder (NRP) subgroups. The results from experiment I showed that packed cell volume (PCV) and plasma albumin concentration were significantly lower in CKD dogs of all stages while the total iron binding capacity (TIBC) was lower in only CKD stage 3 and 4 compared with dogs in CONT group. The PCV was related to both TIBC and albumin when considering among all dogs or only in CKD dogs. The hepcidin concentration in CKD dogs with anemia was lower than those without anemia (P<0.05). In experiment II before darbepoetin alfa treatment, RP subgroup had significantly higher iron and TIBC compared with NRP subgroup (P<0.05), the iron concentration was decreased only in RP subgroup after darbepoetin alfa treatment (P<0.05). The percent increase in PCV was correlated with initial TIBC (P<0.01). Plasma hepcidin concentration was not different between CONT and CKD groups and between RP and NRP subgroups both before and after darbepoetin alfa treatment. It is concluded that TIBC and plasma iron concentration play role on anemia and erythropoietic response to darbepoetin alfa treatment in CKD dogs.
Topics: Animals; Darbepoetin alfa; Dog Diseases; Dogs; Erythropoiesis; Erythropoietin; Hemoglobins; Iron; Renal Insufficiency, Chronic
PubMed: 33563860
DOI: 10.1292/jvms.20-0574 -
Molecular Biotechnology Sep 2016Darbepoetin alfa is a biopharmaceutical glycoprotein that stimulates erythropoiesis and is used to treat anemia, which associated with renal failure and cancer...
Darbepoetin alfa is a biopharmaceutical glycoprotein that stimulates erythropoiesis and is used to treat anemia, which associated with renal failure and cancer chemotherapy. We herein describe the structural characterization of recombinant darbepoetin alfa produced by Leishmania tarentolae T7-TR host. The DNA expression cassette was integrated into the L. tarentolae genome through homologous recombination. Transformed clones were selected by antibiotic resistance, diagnostic PCRs, and protein expression analysis. The structure of recombinant darbepoetin alfa was analyzed by isoelectric focusing, ultraviolet-visible spectrum, and circular dichroism (CD) spectroscopy. Expression analysis showed the presence of a protein band at 40 kDa, and its expression level was 51.2 mg/ml of culture medium. Darbepoetin alfa have 5 isoforms with varying degree of sialylation. The UV absorption and CD spectra were analogous to original drug (Aranesp), which confirmed that the produced protein was darbepoetin alfa. Potency test results revealed that the purified protein was biologically active. In brief, the structural and biological characteristics of expressed darbepoetin alfa were very similar to Aranesp which has been normally expressed in CHO. Our data also suggest that produced protein has potential to be developed for clinical use.
Topics: Circular Dichroism; Cloning, Molecular; Darbepoetin alfa; Leishmania; Molecular Weight; Protein Isoforms; Recombinant Proteins
PubMed: 27282622
DOI: 10.1007/s12033-016-9954-x -
Darbepoetin alfa administered once monthly maintains haemoglobin levels in stable dialysis patients.Nephrology, Dialysis, Transplantation :... Apr 2004Darbepoetin alfa, a glycoprotein that stimulates erythropoiesis by the same mechanism as endogenous erythropoietin, has a 3-fold longer terminal half-life than... (Clinical Trial)
Clinical Trial
BACKGROUND
Darbepoetin alfa, a glycoprotein that stimulates erythropoiesis by the same mechanism as endogenous erythropoietin, has a 3-fold longer terminal half-life than recombinant human erythropoietin, allowing for an extended dosing interval. Darbepoetin alfa is currently recommended for once-weekly and once every 2 weeks administration in patients with chronic renal failure (CRF). The objective of this study was to explore once-monthly administration in this patient population.
METHODS
Clinically stable dialysis patients (mean haemoglobin concentration, 10.0-13.0 g/dl) receiving stable darbepoetin alfa therapy administered once every 2 weeks in a long-term treatment study were converted to darbepoetin alfa once every 3 weeks for 20 weeks and then, if haemoglobin concentrations were successfully maintained between 10.0 and 13.0 g/dl, were converted to darbepoetin alfa once every 4 weeks for 20 weeks. The darbepoetin alfa dose was titrated to maintain haemoglobin within a target range (-1.0 to +1.5 g/dl of baseline haemoglobin, and between 10.0 and 13.0 g/dl). Success with the extended dosing interval was defined as maintenance of mean haemoglobin >/=10.0 g/dl during a 4-week evaluation at the end of the dosing period.
RESULTS
Of the 54 patients who entered the study, 38 patients were converted to darbepoetin alfa administered once every 4 weeks. Of these, 36 patients were considered evaluable and 30 (83%) of those evaluable patients successfully maintained the target haemoglobin. For successful patients the mean (SD) haemoglobin during evaluation was 11.16 (0.60) g/dl, and the mean change in haemoglobin from baseline to evaluation was -0.26 g/dl (95% CI: -0.51, -0.01). The median change from baseline in average weekly darbepoetin alfa dose was 1.61 microg (95% CI: 0.00, 4.75). Adverse events were consistent with those expected for this patient population.
CONCLUSIONS
Darbepoetin alfa, administered once monthly, maintained haemoglobin effectively and safely in most dialysis patients stabilized previously on once every 2 weeks dosing. Once-monthly dosing may optimize anaemia management for patients with CRF and for health care providers.
Topics: Aged; Anemia; Darbepoetin alfa; Dose-Response Relationship, Drug; Drug Administration Schedule; Erythropoietin; Female; Hemoglobins; Humans; Male; Renal Dialysis
PubMed: 15031347
DOI: 10.1093/ndt/gfh021