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Aim: Darbepoetin alpha is available as Aranesp® and NESP®, which differ in the inactive component and maximum dose‐strength of prefilled syringes. We conducted an observational cohort study to investigate optimal conversion strategies and the feasibility of extending dosing intervals with higher‐dose preparations in dialysis patients converting from Aranesp® to NESP®. Methods: Adult dialysis patients on Aranesp® with stable haemoglobin of 9–12 g/dL were converted to NESP® at the same monthly total dose according to one of three conversion regimens. Group A included patients on ≤80 mcg/month of Aranesp® who converted with dosing regimen unchanged. Group B patients converted to NESP® with extended dosing intervals using higher individual dose preparations. Group C were patients on 100 mcg Aranesp® who converted to NESP® 120 mcg with extended dosing intervals. Patients were observed for 6 months. Results: Fifty patients were included. All 24 Group A patients maintained stable haemoglobin. In Group B, 10 patients (50%) maintained stable haemoglobin with extension of dosing interval from 1.04 ± 0.14 to 3.03 ± 1.28 weeks. Factors associated with success in extending dosing interval included a lower prevalence of cardiovascular disease and a higher Kt/Vurea in peritoneal dialysis patients. Four patients (80%) in Group C maintained stable haemoglobin after conversion to NESP® 120 mcg with extended dosing interval. The use of NESP® 120 mcg was well tolerated, and was associated with reduced patient‐reported pain score and 38% reduction of drug cost. Conclusion: Dialysis patients on Aranesp® can be successfully converted to NESP® and the dosing interval can be extended successfully in a significant proportion of patients, which could reduce discomfort and drug cost. SUMMARY AT A GLANCE: This prospective study showed that a substantial proportion of dialysis patients treated with Aranesp® could be successfully converted to NESP®. The dosing interval could be extended, which would reduce discomfort and drug cost. [ABSTRACT FROM AUTHOR]

Aim Erythropoiesis-stimulating agent (ESA) treatment during the predialysis period can be a strategy to reduce cardiac mortality soon after initiation of dialysis. In this study, we compared the efficacy of continuous erythropoietin receptor activator (CERA) and darbepoetin alfa (DA) in patients with chronic kidney disease (CKD) over 6 months prior to initiation of dialysis. Methods This study was a retrospective propensity score-matched study conducted at a single center in Japan that analyzed the effects of CERA and DA therapy on haemoglobin (Hb) changes, ESA resistance index (ERI) changes, and interval of ESA administration during a 6-month observation period prior to initiation of dialysis. Propensity scores were used for matching the patients included in the CERA and DA groups. Results Among 680 screened, 74 pairs of patients (one in each group) were included in the present analysis after propensity score matching. Mean Hb significantly decreased over 6 months in the DA group compared to that in the CERA group (−0.70 ± 0.23 vs. -0.33 ± 0.22). In the DA group, mean ERI was significantly increased at 4, 3, 2, and 1 month before dialysis and initiation of dialysis, while in the CERA group, mean ERI was significantly increased only at 1 month before dialysis and initiation of dialysis. Moreover, patients administered CERA were required to visit the hospital significantly less frequently for ESA administration than those administered DA. Conclusion Our study showed that CERA may be more effective than DA for management of anaemia during the predialysis period in CKD patients. [ABSTRACT FROM AUTHOR]

Aim While darbepoetin alfa ( DA) can be administered once monthly ( QM) to maintain haemoglobin ( Hb) concentrations in anaemic patients with chronic kidney disease not on dialysis ( CKD-ND), the QM use of DA for anaemia correction has not been previously investigated. Methods In this randomized, double-blind, non-inferiority, active-controlled study, adult subjects with CKD-ND, Hb levels <10 g/dL, and not treated with an erythropoiesis-stimulating agent were randomized 1:1 to receive DA every 2 weeks ( Q2 W) or QM for 33 weeks with initial doses of 0.75 μg/kg Q2 W or 1.5 μg/kg QM. Subjects were treated to target Hb levels of 10-12 g/dL and ≥1 g/dL increase from baseline. The primary end-point was Hb change between baseline and the evaluation period (weeks 29-33), with a non-inferiority margin of −0.5 g/dL. Results Three hundred and fifty-five subjects received ≥1 dose of DA. Mean (95% confidence interval [ CI]) change in Hb between baseline and the evaluation period was 2.16 (1.98-2.33) g/dL for the Q2 W group and 1.97 (1.80-2.14) g/dL for the QM group, the mean (95% CI) difference in Hb change being −0.19 (−0.43 to 0.05) g/dL. Most subjects (97.9% Q2 W; 98.1% QM) achieved a Hb level ≥10.0 g/dL and ≥1.0 g/dL increase in Hb from baseline. Mean DA ( SD) weekly equivalent doses over the evaluation period were 0.20 (0.23) and 0.27 (0.31) μg/kg per week for the Q2 W and QM groups, respectively. Safety profiles were similar between groups. Conclusion In subjects with CKD-ND, QM dosing was non-inferior to Q2 W dosing for anaemia correction and had a similar safety profile. [ABSTRACT FROM AUTHOR]

Aim To investigate methoxy polyethylene glycol-epoetin beta dosing regimen in treatment naïve subjects and dose conversion in darbepoetin alpha treated subjects, in Chinese dialysis patients. Methods Adult Chinese patients on peritoneal dialysis ( PD) or haemodialysis ( HD), with no prior treatment with erythropoiesis-stimulating agents and haemoglobin below 8 g/d L ( Group I) or receiving darbepoetin alpha and had stable haemoglobin at 10-12 g/d L ( Group II) were included in this prospective open-label study. In Group I methoxy polyethylene glycol-epoetin beta was started at 0.6 μg/kg subcutaneously fortnightly till haemoglobin reached 10 g/d L, after which it was given monthly. A dose conversion table was devised for Group II. Follow-up was 36 weeks. Results Forty-five patients were included. Haemoglobin in Group I ( n = 23, PD/ HD:19/4) increased from 7.5 ± 0.9 g/d L at baseline to 10.7 ± 1.0 g/d L after 16 weeks, while it remained stable at 10.4 ± 1.0 g/d L after conversion in Group II ( n = 22, PD/ HD:15/7). Actual dose required after stabilization was 1.7 μg/kg per month in Group I and 2.3 μg/kg per month in Group II. Median number of dose adjustment was three in Group I and one in Group II, while haemoglobin overshoot to 13 g/d L or above occurred in 4.4% and 9.1%, respectively. No significant side-effect was observed. Conclusions Our dosing regimen for methoxy polyethylene glycol-epoetin beta, for treatment naïve subjects or for conversion from darbepoetin alpha, is safe and effective. The dose required to achieve a haemoglobin concentration of 10-11 g/d L in Chinese dialysis patients is approximately 2 μg/kg monthly. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

This study aimed to compare the within-patient variability in haemoglobin levels in haemodialysis patients receiving intravenous epoetin alfa or intravenous darbepoetin alfa. Data on haemodialysis patients were extracted from the Renal Anaemia Management database from 2003 to 2004. The variance in haemoglobin was calculated for each patient with more than five haemoglobin observations ( n = 3619). A mixed model was fitted to the within-patient variances and weighting was based on the number of observations minus 1 for each patient. The model took into account the situation where patients had data on both agents and could therefore act as their own control. The mean within-patient variance in haemoglobin levels for patients receiving darbepoetin alfa was 24% (95% CI: 18%, 31%) greater than that for patients receiving epoetin alfa ( P < 0.0001). The mean haemoglobin level for patients receiving darbepoetin alfa was 11.33 g/dL (95% CI: 11.27, 11.40) compared with 11.43 g/dL (95% CI: 11.39, 11.46) for patients receiving epoetin alfa ( P < 0.01). There was greater within-patient fluctuation in haemoglobin levels in patients receiving darbepoetin alfa compared with epoetin alfa. The implications of haemoglobin fluctuations on patient outcomes and resource use require further study. [ABSTRACT FROM AUTHOR]

Aim: The purpose of the present study was to determine whether Australian haemodialysis patients receiving intravenous epoetin alfa are comparable to those receiving darbepoetin alfa with respect to a range of demographic and clinical characteristics. Methods: Data on haemodialysis patients were extracted from the Renal Anaemia Management database for the period from July 2003 to March 2004. Results: Patients on haemodialysis were more likely to receive epoetin alfa than to receive darbepoetin alfa ( n = 1898 vs n = 603, respectively). Patients receiving epoetin alfa were marginally older than patients receiving darbepoetin alfa (61 ± 15 vs 59 ± 15, mean ± SD; P < 0.05). Patients were similar in terms of proportion of males, incidence of diabetes, and angiotensin-converting enzyme inhibitor and antihypertensive use. However, patients receiving epoetin alfa had higher haemoglobin (116 ± 13 g/L vs 113 ± 15 g/L), serum ferritin (582 ± 414 μg/L vs 461 ± 350 μg/L) and transferrin saturation levels (29 ± 13% vs 26 ± 14%), and better dialysis adequacy test results, as measured by urea reduction ratio (URR) or Kt/V, than patients on darbepoetin alfa ( P < 0.001 in all cases). The frequency of dosing was higher in the epoetin alfa group (1.7 ± 0.7 doses/week vs 1.0 ± 0.4 doses/week, P < 0.001). Using the 240:1 dose ratio recommended in the Australian prescribing information for darbepoetin alfa, epoetin alfa was administered at a lower dose compared with darbepoetin alfa (164 ± 116 IU/kg per week vs 192 ± 152 IU/kg per week, P < 0.001). Conclusion: This cross-sectional sample of Australian clinical practice suggests that there are differences in the haematological parameters of patients receiving epoetin alfa compared with patients receiving darbepoetin alfa. [ABSTRACT FROM AUTHOR]

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 enrolment. 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 0e; 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 0e; 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 μg. 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. [ABSTRACT FROM AUTHOR]

The recommended conversion dose for changing from epoetin alfa to darbepoetin alfa is 200 units to 1 µg. However, this may result in the over treatment of uraemic anaemia.All in-centre haemodialysis patients (n = 60) were converted from an existing subcutaneous epoetin alfa regimen to weekly intravenous darbepoetin alfa. The protocol for anaemia management included a target haemoglobin (Hb) concentration of 120–130 g/L and a ferritin of 300–600 µg/L. Patient treatments were converted from subcutaneous epoetin alfa to weekly, intravenous darbepoetin alfa at month 0, at a conversion dose of 200 units epoetin alfa to 1 µg darbepoetin.Both Hb and ferritin concentrations remained within the target range, but darbepoetin dosages fell from 50.8 to 42.3 µg/week by month 3 (P = 0.02). The initial conversion factor of 210 units/µg rose to 275 units/µg (P = 0.01) at month 4. No difference in conversion dosage could be determined between patients who were epoetin sensitive (<200 units/kg per week) or resistant (>200 units/kg per week,P = NS). Patients were then switched to fortnightly darbepoetin alfa dosing treatments; the existing weekly dose being doubled and Hb levels fell from 125 to 110 g/L (P < 0.0001), despite an increase in the mean dose from 44.9 to 47.5 µg/week (P = 0.02).The original dosage reduction after the switch from epoetin alfa to weekly intravenous darbepoetin alfa may offset the increased relative cost of the latter. When administered weekly and intravenously, darbepoetin alfa maintains Hb at a more favourable conversion rate than is currently recommended. [ABSTRACT FROM AUTHOR]

SUMMARY Darbepoetin alfa (Aranesp® , Amgen Ltd) is a long-acting, hyperglycosylated recombinant human erythropoietin (r-HuEPO; epoetin) analogue, developed for the treatment of anaemia in patients with chronic kidney disease (CKD, i.e. end-stage renal failure or progressive renal impairment). Based on previously published European guidelines, this review article presents key recommendations for the use of darbepoetin alfa in Australasian clinical practice. Darbepoetin alfa is expected to be a valuable alternative therapeutic agent for the management of renal anaemia. Clinical data demonstrate that: Once-weekly administration of darbepoetin alfa – whether by subcutaneous (s.c.) or intravenous (i.v.) injection – is as effective as epoetin therapy, administered two or three times per week; patients receiving once-weekly doses of epoetin can be switched to darbepoetin alfa, once every 2 weeks; target haemoglobin (Hb) concentrations can be successfully maintained in patients switched from epoetin therapy to less frequently administered doses of darbepoetin alfa (administration once every 2 weeks is sufficient for some patients); and darbepoetin alfa has a similar safety profile to epoetin. In addition to addressing a number of practical considerations relating to the use of darbepoetin alfa in clinical practice, this article also highlights principal findings from several key clinical studies. [ABSTRACT FROM AUTHOR]

The article presents a study on the effects of Erythropoiesis-Stimulating Agents including darbepoetin alfa, continuous erythropoietin receptor agonists (CERA) and recombinant human erythropoietin (rHuEPO) preparations on mortality rates, hypertension and haemodialysis access thrombosis. No significant difference is reported in the review published originally in 2002 and updated in 2005. Effect of change in frequency of administration of stimulants also was studied.