Randomized trial of darbepoetin alfa for treatment of renal anemia at a reduced dose frequency compared with rHuEPO in dialysis patients

BACKGROUND: Darbepoetin alfa is a glycoprotein with a three-fold longer terminal half-life than recombinant human erythropoietin (rHuEPO). We aimed to determine whether darbepoetin alfa is as effective and well tolerated as rHuEPO for treating renal anemia in dialysis patients when administered at a reduced dose frequency. METHODS: A total of 522 European and Australian hemodialysis and peritoneal dialysis patients receiving stable rHuEPO therapy by either the intravenous (IV) or subcutaneous (SC) route were randomized, open-label in a 1:2 ratio to continue rHuEPO or to receive an equivalent dose of darbepoetin alfa at a reduced dose frequency. Patients receiving rHuEPO once weekly changed to once every other week darbepoetin alfa, and those receiving rHuEPO two or three times weekly changed to once-weekly darbepoetin alfa. The doses of rHuEPO and darbepoetin alfa were titrated to maintain hemoglobin close to the patient's baseline level for up to 52 weeks. The primary endpoint was the change in hemoglobin between baseline and the evaluation period at weeks 25 to 32 of treatment. RESULTS: The mean change in hemoglobin from baseline to the evaluation period was similar in the darbepoetin alfa (-0.03 g/dL; SE 0.11) and rHuEPO (-0.06 g/dL; SE 0.13) groups, and the difference between the two treatments was 0.03 g/dL (95% CI -0.16, 0.21). This was not a statistically significant or clinically relevant difference, despite the reduced frequency of darbepoetin alfa administration. At the end of the evaluation period, >/=95% of patients had their hemoglobin successfully maintained on their assigned dose frequency for darbepoetin alfa (once weekly and once every other week) and rHuEPO (once, twice and three times weekly). The safety profiles of darbepoetin alfa and rHuEPO were similar, and no antibodies to either treatment were detected. CONCLUSIONS: Darbepoetin alfa maintains hemoglobin as effectively as rHuEPO, but with a reduced dose frequency.     

Darbepoetin-alfa treatment of anemia secondary to chronic renal failure in dialysis patients: Results of a French multicenter study

Darbepoetin alfa is a unique genetically engineered glycoprotein with a three-fold longer terminal half-life than recombinant human erythropoietin (rHuEPO). The objective of this study was to determine if darbepoetin alfa administered at a reduced dosing frequency relative to the prior rHuEpo regimen is an effective and safe alternative for treating renal anemia in patients undergoing dialysis. A total of 1,008 French hemodialysis and peritoneal dialysis patients receiving stable rHuEPO therapy by either the intravenous (i.v., N = 217) or subcutaneous (s.c., N = 791) route were switched to darbepoetin alfa given by the same route of administration at a reduced dosing frequency. Patients receiving rHuEPO once weekly (N = 248, 25%) were switched to darbepoetin alfa every two weeks, and those receiving rHuEPO two or three times weekly (N = 760, 75%) were switched to darbepoetin alfa once weekly. The doses of darbepoetin alfa were titrated to maintain hemoglobin concentration in the target range of 10.0 to 13.0 g/dl for up to 24 weeks. The primary endpoint was the change in hemoglobin between baseline and the evaluation period (weeks 21-24). Adjusted (for covariates that might influence hemoglobin response) mean change in hemoglobin from baseline to the evaluation period was not clinically significant: +0.11 g/dl (95% CI: -0.30; 0.52). An i.v./s.c. dose ratio of 0.96 (95% CI: 0.86; 1.06) at evaluation confirms previous findings that darbepoetin alfa dose requirements were not different for the s.c. and i.v. routes. At the end of the evaluation period, more than 98% of patients successfully maintained hemoglobin within the target range and at their darbepoetin alfa assigned dosing frequency. Darbepoetin alfa was well tolerated with a safety profile consistent with that observed in previous darbepoetin alfa studies. Darbepoetin alfa administered at a reduced dosing frequency relative to the prior rHuEpo regimen effectively maintains hemoglobin in the target range in dialysis patients with renal anemia.     

Darbepoetin alfa administered every other week maintains hemoglobin levels over 52 weeks in patients with chronic kidney disease converting from once-weekly recombinant human erythropoietin: results from simplify the treatment of anemia with Aranesp (STAAR)

BACKGROUND/AIM: Darbepoetin alfa, an effective treatment for anemia of chronic kidney disease (CKD), can be administered at extended intervals. Simplify the Treatment of Anemia with Aranesp (STAAR), a multicenter, 52-week study, was conducted to assess the efficacy of darbepoetin alfa administered subcutaneously every other week (Q2W) in maintaining hemoglobin (Hb) in CKD patients not receiving dialysis. METHODS: This is a subgroup analysis of subjects converted from once-weekly (QW) recombinant human erythropoietin (rHuEPO; US Aranesp package insert) and who received up to 52 weeks of darbepoetin alfa therapy (evaluation period 20-32 weeks). Enrolled subjects had a creatinine clearance < or = 70 ml/min or an estimated glomerular filtration rate < or = 60 ml/min and transferrin saturation > or = 20%. Darbepoetin alfa doses were titrated to maintain Hb levels < or = 12 g/dl. The primary endpoint was mean Hb during evaluation. RESULTS: There were 524 subjects enrolled in the study who were previously receiving rHuEPO QW. Mean Hb +/- standard deviation was 11.2 +/- 1.27 g/dl at baseline, and the least squares mean +/- SE was 11.4 +/- 0.04 during evaluation. The mean +/- SD Q2W darbepoetin alfa dose was 49.7 +/- 21.9 microg at baseline and 48.9 +/- 35.5 microg at evaluation. Darbepoetin alfa was well tolerated. CONCLUSIONS: Study subjects with CKD receiving QW rHuEPO were effectively converted to Q2W darbepoetin alfa, which was well tolerated. Hb levels were maintained over 52 weeks without a significant change in darbepoetin alfa dose.     

Darbepoetin alfa administered once monthly maintains hemoglobin concentrations in patients with chronic kidney disease

BACKGROUND: Darbepoetin alfa is an erythropoiesis-stimulating glycoprotein that functions by the same mechanism as recombinant human erythropoietin (rHuEPO), but has a three-fold longer serum half-life. Reduction in the frequency of darbepoetin alfa administration would be beneficial to patients with renal disease and their healthcare providers. This study evaluated the effect of extending the darbepoetin alfa dosing interval to once monthly in patients with chronic kidney disease (CKD) not receiving dialysis. METHODS: This study was a multicenter, open-label study of 97 patients with CKD not on dialysis. Patients receiving stable subcutaneous doses of darbepoetin alfa once every two weeks were converted to darbepoetin alfa once monthly for 29 weeks. The proportion of patients who successfully maintained hemoglobin concentrations between 10.0 and 12.0 g/dl and the mean darbepoetin alfa dose were evaluated. Safety measurements (e.g. adverse events, laboratory parameters, blood pressure) and seroreactivity were assessed. RESULTS: Hemoglobin concentration was maintained within the target range in 79% (95% confidence interval (CI) = 71% to 87%) of all patients receiving darbepoetin alfa and in 85% (95% Cl = 78% - 93%) of patients who completed the study period. The mean +/- standard deviation monthly darbepoetin alfa dose was similar between baseline (88.7 +/- 49.9 microg) and the evaluation period (86.6 +/- 78.8 microg). The safety profile for monthly darbepoetin alfa administration was comparable with that previously observed with more-frequent administration. CONCLUSION: Patients with CKD who are clinically stable on darbepoetin alfa administered once every two weeks can be safely and effectively converted to darbepoetin alfa administered once monthly.     

Treatment of anemia with darbepoetin alfa administered de novo once every other week in chronic kidney disease

BACKGROUND/AIMS: Darbepoetin alfa is an erythropoiesis-stimulating protein that works via the same mechanism and has a threefold longer serum half-life than recombinant human erythropoietin (rHuEPO). The objective of this study was to evaluate extending the dosing interval of darbepoetin alfa to once every other week administration for the treatment of anemia in patients with chronic kidney disease (CKD) not requiring dialysis who were naive to rHuEPO therapy. METHODS: This was a multi-center, open-label study. Seventy-six rHuEPO-naive patients were enrolled to receive darbepoetin alfa (0.75 microg/kg) once every other week for up to 24 weeks. Doses were titrated to achieve and maintain a hemoglobin target of 11.0 to 13.0 g/dl. RESULTS: Ninety-seven percent (95% CI: 0.92, 1.00) of patients completing 24 weeks of treatment achieved a hemoglobin response. The median time to response was 5 weeks (range 1-25 weeks). The median darbepoetin alfa dose at the time of response was 60 microg(range 30-130 microg). Darbepoetin alfa was safe and well tolerated, and no antibodies to darbepoetin alfa were detected. CONCLUSION: These results demonstrate the utility of darbepoetin alfa administered once every other week in rHuEPO-naive CKD patients. This new treatment paradigm may allow for more widespread management of anemia in patients with CKD.     

Treatment of anaemia in dialysis patients with unit dosing of darbepoetin alfa at a reduced dose frequency relative to recombinant human erythropoietin (rHuEpo).

BACKGROUND: Darbepoetin alfa is an erythropoietic agent with a 3-fold longer elimination half-life than recombinant human erythropoietin (rHuEpo), which allows less frequent dosing. This study investigated the safety and efficacy of darbepoetin alfa for treating anaemia in dialysis patients, using a dosing regimen that was independent of the patient's body weight (unit dosing). METHODS: Dialysis patients (n=341) maintained on rHuEpo treatment (alfa or beta) were switched to darbepoetin alfa at a reduced dosing frequency, but by the same route of administration [intravenous (i.v.) or subcutaneous (s.c.)]. Patients receiving rHuEpo two or three times weekly changed to once-weekly darbepoetin alfa, and those receiving rHuEpo once weekly changed to once every other week darbepoetin alfa. The unit doses of darbepoetin alfa (10-150 microg) were titrated to maintain haemoglobin concentrations within -1.0 and +1.5 g/dl of the individual mean baseline haemoglobin and between 10 and 13 g/dl for 24 weeks. RESULTS: Mean change in haemoglobin from baseline to the evaluation period (weeks 21-24) was 0.13 g/dl (95% CI, 0.01, 0.25), which was not clinically relevant. An analysis by route of administration revealed that mean haemoglobin concentrations had increased by 0.58 g/dl (95% CI, 0.33, 0.82) in patients receiving i.v. darbepoetin alfa, and previously treated with i.v. rHuEpo, while remaining unchanged in s.c. patients (0.00 g/dl; 95% CI, -0.13, 0.13) previously treated by s.c. rHuEpo. In addition, there was a statistically significant decrease in mean weekly i.v. darbepoetin alfa dose requirements from 25.2 microg/week at baseline to 21.5 microg/week (P=0.004) during the evaluation period (-17.3%). Subcutaneous weekly dosage requirements increased slightly during the study period (20.8 to 22.7 microg/week; P=0.014). An i.v./s.c. dose ratio of 0.95 (95% CI, 0.78, 1.14) at evaluation confirms previous findings that dose requirements by the i.v. and s.c. routes were not different in patients treated with darbepoetin alfa. Haemoglobin concentrations were also effectively maintained in patients who received darbepoetin alfa once weekly and once every other week. Darbepoetin alfa was well tolerated. CONCLUSIONS: The treatment of renal anaemia in dialysis patients with unit doses of darbepoetin alfa effectively and safely maintains target haemoglobin concentrations with less frequent dosing. Dose requirements for darbepoetin alfa following i.v. and s.c. administration were not different. The results of this study demonstrate that darbepoetin alfa administered i.v. once weekly, or once every other week is an effective treatment regimen for haemodialysis patients with renal anaemia.     

Darbepoetin alfa effectively treats anemia in patients with chronic kidney disease with de novo every-other-week administration

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.     

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.     

Darbepoetin alfa once every 2 weeks for treatment of anemia in dialysis patients: a combined analysis of eight multicenter trials

AIM: Darbepoetin alfa has a longer half-life than epoetin-(EPO) alfa or beta, allowing administration at less frequent intervals for the treatment of renal anemia. The aim of the present analysis was to evaluate the efficacy and tolerability of an every-2-week (Q2W) schedule of darbepoetin alfa in a large cohort of dialysis patients. METHODS: Data were combined from eight similarly designed 24-week phase 3b European studies, in which patients receiving EPO alfa or beta once-weekly were converted to Q2W darbepoetin alfa. Darbepoetin alfa dosage was titrated to maintain hemoglobin (Hb) between 10 and 13 g/dl and efficacy was evaluated during a 4-week evaluation period. RESULTS: In the 1,101 patients assigned to Q2W darbepoetin alfa (i.v., n = 196, s.c., n = 905), mean (SD) Hb levels were 11.53 (0.77) g/dl at baseline and 11.35 (1.04) g/dl at evaluation (mean change in Hb -0.27 g/dl, 95% confidence interval 0.34, -0.20). Hb levels were maintained between 10 and 13 g/dl during evaluation in 85% of patients. Darbepoetin alfa doses were similar at baseline and evaluation, and the i.v. and s.c. routes were associated with similar efficacy and dose requirements. Darbepoetin alfa was well-tolerated. CONCLUSIONS: Q2W darbepoetin alfa is effective in maintaining Hb levels in dialysis patients switched from weekly rHuEPO, regardless of the route of administration and with no notable increase in the weekly equivalent dose.     

Darbepoetin alfa administered once monthly maintains haemoglobin levels in stable dialysis patients.

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.     

Efficacy and safety of once-weekly intravenous epoetin alfa in maintaining hemoglobin levels in hemodialysis patients

BACKGROUND: Although an erythropoiesis-stimulating agent (ESA) is most frequently administered intravenously for treatment of anemia in patients with chronic kidney disease who are on dialysis, few studies have compared the efficacy of different intravenous (i.v.) dosing schedules. METHODS: This multicenter, phase IIIb, open-label, controlled study randomized 289 stable hemodialysis patients to continue with conventional dosing of i.v. epoetin alfa or darbepoetin, or to switch to once-weekly i.v. epoetin alfa at the same cumulative weekly starting dose, to maintain hemoglobin levels at 11.0-13.0 g/dL, and within 1.0 g/dL of the baseline value. Hemoglobin levels and ESA doses were recorded every 4 weeks for 28 weeks. RESULTS: Hemoglobin levels fell significantly and ESA doses increased significantly between baseline and week 28 (mean of week 16-28 values) in the once-weekly epoetin alfa group, compared with the conventional treatment group (p< 0.001). The adjusted difference in mean hemoglobin levels between the groups was 0.73 g/dL (greater than the threshold for therapeutic equivalence of 0.5 g/dL). The changes between groups from baseline was significant at all time points for hemoglobin levels (0.36, 0.46, 0.81, 0.87, 0.78, 0.62 and 0.49 g/dL) and from week 12 for ESA dose (718.5, 1,326.5, 1,732.0, 1,839.7 and 1,959.1 IU/week; p=0.005). Hemoglobin was maintained at the target level in 78% and 84% of patients on conventional dosing, and 67% and 64% of those on once-weekly epoetin alfa in the intention-to-treat (p=0.1) and per protocol (p=0.016) populations, respectively. CONCLUSIONS: This study did not show therapeutic equivalence of once-weekly i.v. epoetin alfa with conventional dosing regimens.     

Darbepoetin alfa administered monthly maintains haemoglobin concentrations in patients with chronic kidney disease not receiving dialysis: a multicentre, open-label, Australian study

AIM: Darbepoetin alfa, an erythropoiesis-stimulating protein, has a longer serum half-life than recombinant human erythropoietin, allowing less-frequent administration. This study aimed to demonstrate that once-monthly (QM) darbepoetin alfa administration would maintain haemoglobin (Hb) concentrations in subjects with chronic kidney disease (CKD) not receiving dialysis who had previously been administered darbepoetin alfa every 2 weeks (Q2W). METHODS: This was a multicentre study in which subjects with CKD receiving stable Q2W darbepoetin alfa doses and with stable Hb (100-130 g/L) were started on QM darbepoetin alfa dosing. The initial QM darbepoetin alfa dose was equivalent to the cumulative darbepoetin alfa dose administered during the month preceding enrollment. Darbepoetin alfa doses were titrated to maintain Hb concentrations between 100 and 130 g/L. The primary endpoint was the proportion of subjects maintaining mean Hb >or= 100 g/L during the evaluation period (weeks 21-33). RESULTS: Sixty-six subjects were enrolled in the study and all received at least one dose of darbepoetin alfa; 55 (83%) had mean Hb >or= 100 g/L during evaluation. Mean (SD) Hb concentrations at baseline and during the evaluation period were 119 (8.7) g/L and 114 (9.8) g/L, respectively. The median QM darbepoetin alfa dose at baseline and during the evaluation period was 80 microg. Darbepoetin alfa was considered to be well-tolerated. CONCLUSION: Patients with CKD not receiving dialysis who are receiving darbepoetin alfa Q2W can be safely and effectively extended to darbepoetin alfa QM. Dosing QM may simplify anaemia management for patients and health-care providers.     

Correction of anaemia with darbepoetin alfa in patients with chronic kidney disease receiving dialysis.

BACKGROUND: Darbepoetin alfa is a new recombinant erythropoietic protein with a 3-fold longer half-life than recombinant human erythropoietin (rHuEpo). The optimal starting dose and frequency of administration of darbepoetin alfa were investigated for treating renal anaemia in dialysis patients. METHODS: Two multicentre, sequential dose-escalation studies examined the i.v. route of administration of darbepoetin alfa in haemodialysis patients (n=75) and the s.c. route in peritoneal dialysis patients (n=47). Patients were randomized to receive darbepoetin alfa at doses ranging from 0.075 to 0.75 microg/kg/week administered as either a once weekly or a three-times weekly injection. Patients achieving the primary endpoint of a > or = 1 g/dl increase in haemoglobin after 4 weeks continued darbepoetin alfa for up to 52 weeks. Safety was assessed by adverse event reports, changes in laboratory values and vital signs, and antibody screening. RESULTS: Darbepoetin alfa produced dose-related increases in haemoglobin over the first 4 weeks of treatment in both studies. Two dose levels (0.45 and 0.75 microg/kg/week) increased the haemoglobin by > or = 1 g/dl in 60-80% of patients, and no difference between once weekly and three-times weekly dosing was apparent. For patients who continued treatment up to 52 weeks, haemoglobin was maintained between 10 and 13 g/dl from mean baseline values of 8.4 and 8.7 g/dl. The adverse event profile was similar to that associated with rHuEpo therapy, and no antibodies to darbepoetin alfa were detected. CONCLUSIONS: Darbepoetin alfa is safe and effective for the treatment of anaemia in dialysis patients. The optimal weekly starting dose is 0.45-0.75 microg/kg and once weekly dosing is possible for both the s.c. and i.v. routes of administration.     

Intravenously administered darbepoetin alfa once a week could maintain hemoglobin level more efficiently than once every 2 weeks in patients on hemodialysis

Background

Darbepoetin alfa, which has a much longer half-life than recombinant human erythropoietin, is used to treat renal anemia. However, there are few reports investigating the efficacy of darbepoetin alfa administered every 2 weeks (Q2W).

Methods

We performed the single-center, prospective, and randomized study in chronic hemodialysis patients. Clinically stable patients on hemodialysis were recruited, and darbepoetin alfa 15–40 μg/week was administered intravenously once a week (QW) to achieve a hemoglobin (Hb) level of 10.5–12.0 g/dl for 8 weeks prior to randomization. The patients were randomly assigned to 2 different dosing frequency groups: once a week (QW) or every 2 weeks (Q2W). We switched to a double dose in the Q2W group. We measured Hb level every 2 weeks and administered darbepoetin alfa to achieve an Hb level of 10.5–11.5 g/dl. The primary endpoints were the weekly dose of darbepoetin alfa administered at week 24.

Results

We assigned 19 and 20 patients into QW and Q2W, respectively. There were no significant differences between the groups in Hb, transferrin saturation, ferritin, and weekly dose of darbepoetin alfa at end of the baseline period. There was no significant difference in Hb level at week 24, at which time the weekly dose requirement and dose per dry body weight were much higher in the Q2W than in the QW group.

Conclusion

Administration of darbepoetin alfa Q2W could maintain Hb level similarly to to that obtained QW, but we did not confirm efficiency at a higher dose requirement or blood pressure elevation.     

Randomized trial to compare the dosage of darbepoetin alfa by administration route in haemodialysis patients

Aim:   The doses of darbepoetin alfa required to maintain target haemoglobin levels after s.c. or i.v. administration when recombinant human erythropoietin (rHuEpo) treatment was replaced by darbepoetin alfa treatment in haemodialysis (HD) patients were compared.
Methods:   In this prospective, randomized, open-label study, 65 HD patients who were receiving stable SC doses of rHuEpo were switched to an equivalent dose of darbepoetin alfa at a reduced frequency by s.c. or i.v. administration. Patients were randomly assigned to the s.c. group ( n  = 32) or the i.v. group ( n  = 33). Darbepoetin alfa doses were titrated to maintain target haemoglobin levels of 8.0–11.0 g/dL for up to 24 weeks. A period of 20 weeks was used for dose titration and haemoglobin stabilization. This was followed by a 4 week evaluation period.
Results:   The mean haemoglobin concentration during the evaluation period was similar in the s.c. and i.v. groups. The mean dose and mean weight-standardized dose of darbepoetin alfa during the evaluation period tended to be lower in the s.c. group than the i.v. group, although these differences were not statistically significant. The mean weekly darbepoetin alfa dose requirements during the evaluation period significantly decreased in both groups compared to the dose requirements at randomization.
Conclusion:   There is a possibility that s.c. administration of darbepoetin alfa is more efficacious than i.v. administration, but a definite benefit cannot be demonstrated with the current sample size. A bigger sample size is needed to confirm the result.     

Feasibility strategy of darbepoetin alfa administration every other week: 2005-2007 experience in a dialysis unit

Darbepoetin alfa is a recombinant erythropoiesis-stimulating agent, with a longer half-life leaving the possibility to extending dosing administration in haemodialysis patients. A protocol of injection every 2weeks was initiated in the dialysis unit. From 2005 to 2007, 176 dialysis patients were studied with a target haemoglobin level between 11 and 12.5g/dL: the median haemoglobin level was ranged from 11.32 and 11.72g/dL during the study with a median darbepoetin alfa dose injected between 60 and 64μg per injection (0.46 to 0.47μg/kg per week). The mean number of dose changes was three per year per patient. The diabetic population did not differ from the general population in terms of haemoglobin levels and doses of darbepoetin alfa. Ten percent of the patients had to resume one injection per week for medical reasons: the profile of these patients was carefully studied. Hospitalisations resulted in a decrease in haemoglobin level and an increase in the darbepoetin alfa doses. Patients who died showed during the last 3months, a particular profile. Hyporesponsiveness has been explored. Time saving with this protocol was important for all the nursing staff. Although numerous factors of variability have been studied, there still a room for improvement of anemia management in haemodialysis patient.     

Darbepoetin alfa (Aranesp) in children with chronic renal failure

BACKGROUND: Darbepoetin alfa use has been reported in 7 children with chronic renal failure (CRF). Our objective was to evaluate the efficacy and safety of darbepoetin and determine a therapeutic dose in a larger sample of children with CRF. METHODS: Twenty-six children with chronic renal insufficiency (CRI) GFR <30 mL/min/1.73 m(2), on peritoneal dialysis (PD) or hemodialysis (HD) entered a prospective, open-label study of darbepoetin. Seven ineligible children who underwent the same evaluation were analyzed retrospectively. The starting dose was 0.45 microg/kg/week. IRB/REB approval and informed consent were obtained. The primary outcome measure was hemoglobin (Hb) response within a target range of 10.0 to 12.5 g/dL between 8 and 12 and 20 and 28 weeks. RESULTS: Thirty-three children (15 CRI, 9 HD, 9 PD; aged 1-17 years) were enrolled in the study. Ten patients dropped out (3 before 12 weeks and 7 before 28 weeks), none due to darbepoetin. Mean Hbs were 11.8 and 11.4 between weeks 8 and 12 and 20 and 28, respectively; the proportion of patients with Hb values >10.0 g/dL was 97% and 91% in the same intervals. No effect of grouping patients into CRI, HD, or PD or prospective versus retrospective was observed. One of 13 serious adverse events (hypertension) was possibly related to darbepoetin; 8/14 children reported injection-site pain. At 12 and 28 weeks, respectively, 73% and 87% were receiving darbepoetin less than once weekly. CONCLUSION: A dose approximating 0.5 microg/kg/week of darbepoetin effectively treats anemia in children with chronic renal failure; for many, this may be proportionately increased and injected less than once weekly.     

A Retrospective Assessment of Pre-Treatment Variables on the Response to Darbepoetin Alfa After Renal Transplantation

This retrospective review assesses the efficacy of darbepoetin alfa for treating anemia after renal transplantation. Patients were evaluated over a 12-week period, and efficacy was based on achieving hemoglobin >12 g/dL. Thirty-six patients were analyzed (53% male, 53% cadaveric allografts, median age 42.5 years). Baseline creatinine clearance ranged from approximately 15 to >100 mL/min. Most patients initiated darbepoetin alfa <3 months (50%) or >12 months (44%) after transplantation, 19% were previously receiving recombinant human erythropoietin (rHuEPO), and 47% were on concomitant ACE inhibitors. The majority of patients received either tacrolimus- (53%) or cyclosporine- (44%) based immunosuppression. Overall, 29 (81%) patients achieved the hemoglobin target with a mean time to response of 4.4 weeks. Neither the time to anemia onset, previous rHuEPO therapy, concomitant ACE inhibitor, allograft source, immunosuppressive regimen, nor degree of renal function affected the proportion of patients achieving the hemoglobin target, time to response or darbepoetin alfa dose requirement. Patients with anemia >12 months post-transplantation or on concomitant ACE inhibitors required a significantly longer duration of therapy. No adverse events associated with darbepoetin alfa therapy were detected. These results demonstrate that darbepoetin alfa is a safe and effective treatment for anemia in renal transplant recipients.     

Complete switch to darbepoetin in a hemodialysis unit

AIMS: In March 2003, our hemodialysis unit switched all patients from subcutaneous (s.c.) rHuEPO to intravenous (i.v.) darbepoetin. The primary outcome was to assess the efficacy of i.v. darbepoetin to maintain target serum hemoglobin (Hb) compared to s.c. rHuEPO. Secondary outcomes were to evaluate the manufacturer's recommend guidelines for conversion of rHuEPO to darbepoetin, and to assess the cost implications of darbepoetin therapy. METHODS: This was an 18-month open-label observational study of 95 hemodialysis patients. At the time of the switch to darbepoetin (baseline), data were collected retrospectively for six months and prospectively for 12 months, at three-month intervals. The first six months of darbepoetin therapy was considered a dose titration phase, thus, data were analyzed comparing two six-month periods: (-) six months to baseline (rHuEPO phase) and (+) 6-12 months (darbepoetin phase). Doses were titrated to a target Hb of 120-135 g/l. RESULTS: There was no significant difference in Hb between phases at any time point. Mean Hb ranged from 119.6-121.5 g/l for rHuEPO and 121.9-123.4 g/l for darbepoetin. The median darbepoetin dose remained stable throughout the analysis at 30 microg/week while the median dose of rHuEPO rose from 8,000 U/week at minus six months to 9,000 U/week at baseline. Median 12-month cost savings associated with the administration of darbepoetin were estimated at 212,000 dollars. The recommended darbepoetin dose from the manufacturer's conversion table was deemed too low for baseline rHuEPO doses above 17,000 U/week. A more simplified dose conversion nomogram was created. CONCLUSION: Darbepoetin was able to maintain similar serum Hb levels compared to rHuEPO at a substantially reduced cost.     

Use of recombinant erythropoietin in thalassemic patients on dialysis.

We studied the therapeutic benefit of recombinant human erythropoietin (rHuEPO) in dialysis patients with thalassemia minor. Four of the 40 randomly selected patients (22 on hemodialysis [HD], 18 on continuous ambulatory peritoneal dialysis [CAPD]) were identified to be thalassemic prior to a trial of rHuEPO (alpha-thalassemia trait in three and beta-thalassemia minor in one). All patients were initially treated with rHuEPO at a dose of 100 +/- 25 U/kg/wk subcutaneously depending on the hemoglobin level. EPO injections were continued for 16 weeks with further adjustments of the doses according to the hemoglobin level increases attained. All nonthalassemic patients reached a target hemoglobin of 10 g/dL at week 16, with an average maintenance dose of 120 +/- 7.8 U/kg/wk, but the hemoglobin was increased by only 1 g/dL in the thalassemic patients receiving 175 U/kg/wk. Following cessation of rHuEPO therapy for 6 weeks, all four thalassemic patients and 18 randomly selected nonthalassemic patients received a fixed dose of rHuEPO 4,000 U/wk (equivalent to 80 U/kg/wk) for 16 weeks. The hemoglobin remained unchanged in the thalassemic patients, but a progressive and significant increase of hemoglobin was observed in the nonthalassemic patients. At the last phase of the study, the thalassemic patients received rHuEPO at a dose of 100 or 125 U/kg/wk with 4-weekly increments of 25 U/kg/wk until their hemoglobin reached 10 g/dL. One patient developed uncontrolled hypertension with a dose of 150 U/kg/wk, and one reached the target hemoglobin at a dose of 200 U/kg/wk.(ABSTRACT TRUNCATED AT 250 WORDS)