What is the practical conversion dose when changing from epoetin alfa to darbepoetin outside of clinical trials?

BACKGROUND: The recommended conversion dose for changing from epoetin alfa to darbepoetin alfa is 200 units to 1 microg. However, this may result in the over treatment of uraemic anaemia. METHODS: 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 microg/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 microg darbepoetin. RESULTS: Both Hb and ferritin concentrations remained within the target range, but darbepoetin dosages fell from 50.8 to 42.3 microg/week by month 3 (P = 0.02). The initial conversion factor of 210 units/microg rose to 275 units/microg (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 microg/week (P = 0.02). CONCLUSION: 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.     

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.     

Australian haemodialysis patients on intravenous epoetin alfa or intravenous darbepoetin alfa: How do they compare?

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 mug/L vs 461 +/- 350 mug/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.     

Weekly low-dose treatment with intravenous iron sucrose maintains iron status and decreases epoetin requirement in iron-replete haemodialysis patients.

BACKGROUND: Haemodialysis patients need sustained treatment with intravenous iron because iron deficiency limits the efficacy of recombinant human epoetin therapy in these patients. However, the optimal intravenous iron maintenance dose has not been established yet. METHODS: We performed a prospective multicentre clinical trial in iron-replete haemodialysis patients to evaluate the efficacy of weekly low-dose (50 mg) intravenous iron sucrose administration for 6 months to maintain the iron status, and to examine the effect on epoetin dosage needed to maintain stable haemoglobin values in these patients. Fifty patients were enrolled in this prospective, open-label, single arm, phase IV study. RESULTS: Forty-two patients (84%) completed the study. After 6 months of intravenous iron sucrose treatment, the mean ferritin value showed a tendency to increase slightly from 405 +/- 159 at baseline to 490 +/- 275 microg/l at the end of the study, but iron, transferrin levels and transferrin saturation did not change. The haemoglobin level remained stable (12 +/- 1.1 at baseline and 12.1 +/- 1.5 g/dl at the end of the study). The mean dose of darbepoetin alfa could be reduced from 0.75 to 0.46 microg/kg/week; epoetin alfa was decreased from 101 to 74 IU/kg/week; and the mean dose of epoetin beta could be reduced from 148 to 131 IU/kg/week at the end of treatment. CONCLUSIONS: A regular 50 mg weekly dosing schedule of iron sucrose maintains stable iron stores and haemoglobin levels in haemodialysed patients and allows considerable dose reductions for epoetins. Low-dose intravenous iron therapy may represent an optimal approach to treat the continuous loss of iron in dialysis patients.     

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.     

The efficacy and safety of once-weekly and once-fortnightly subcutaneous epoetin beta in peritoneal dialysis patients with chronic renal anaemia.

BACKGROUND: Reducing the dosage frequency of subcutaneous epoetin in peritoneal dialysis (PD) patients is convenient and should improve patient satisfaction and, possibly, compliance. We investigated if a weekly dosage of epoetin beta in PD patients safely maintained haemoglobin (Hb) concentrations equivalent to those obtained with previous twice- or thrice-weekly administration. In addition, we investigated if a fortnightly dosage of epoetin beta was safe and as effective as previous weekly administration. METHODS: After a 4 week run-in period, PD patients were switched to either weekly or fortnightly epoetin beta administration, depending on their previous treatment schedules, for 25 weeks. RESULTS: The per-protocol cohort included 128 patients, of whom 54 received epoetin beta once weekly and 74 once fortnightly. The mean change in Hb concentration from baseline over weeks 13-25 and the 90% confidence intervals (CIs) remained within the target range (10-12 g/dl) and specified equivalence (+/-0.75 g/dl) limits in the weekly (-0.34 g/dl; 90% CI: -0.14 to -0.54 g/dl) and fortnightly (-0.39 g/dl; 90% CI: -0.24 to -0.55 g/dl) cohorts. The mean change from baseline in the epoetin beta dose was 1.4 IU/kg/week (90% CI: -3.8 to 6.6 IU/kg/week; 2%) in the weekly cohort and 4.4 IU/kg/week (90% CI: 1.7-7.2 IU/kg/week; 13%) in the fortnightly cohort. Both treatment regimens were well tolerated. CONCLUSIONS: In stable PD patients switched from twice- or thrice-weekly to weekly epoetin beta treatment, Hb concentrations could be maintained within the specified range over 25 weeks without significant change in their mean epoetin beta doses. In patients switched from weekly to fortnightly treatment, Hb concentrations could also be maintained over 25 weeks. There was a small increase in the mean dose during this period, but >/=50% of patients could be maintained without dose increase. Reducing dosage frequency may improve compliance in PD patients who self-administer their epoetin.     

The use of darbepoetin in infants with chronic renal impairment

Darbepoetin is a newer analogue of epoetin, with a longer half-life, that allows less frequent administration. There are currently no published data available for its use in infants. We report our experience with this drug in infants with chronic renal impairment, weighing less than 8 kg. Infants had baseline haemoglobin (Hb), iron, ferritin and transferrin levels measured. They were started on approximately 0.5 μg/kg per week of darbepoetin. Hb levels were checked every 2–4 weeks, and iron studies were performed every 4 weeks. Iron supplementation was prescribed to maintain ferritin levels >100 μg/l and transferrin saturation levels >20%. Follow up was for 20 weeks. Six infants with a mean weight of 4.08 kg and a mean creatinine of 259 μmol/l were included. Three infants were medically stable throughout the study, and the mean darbepoetin dose was decreased to 0.25 μg/kg per week. Their dosing interval was increased to every 3–4 weeks. The other three infants were less stable and had multiple medical problems, including periods of haemodialysis and surgery. These infants failed to reach target Hb level, despite an increase in the mean dose of darbepoetin to 1.2 μg/kg per week. In conclusion, darbepoetin can be successfully administered to infants with chronic renal insufficiency, but the dose needs to be tailored to each individual. Administration would be facilitated by smaller unidose syringes.     

The efficacy of intravenous darbepoetin alfa administered once every 2 weeks in chronic kidney disease patients on haemodialysis.

BACKGROUND: It is becoming increasingly more common to administer intravenous (i.v.) darbepoetin alfa to haemodialysis (HD) patients at less frequent dosing intervals in routine clinical practice. This study investigated extending the dosing interval for i.v. darbepoetin alfa treatment from once a week (QW) to once every 2 weeks (Q2W) at the same dose in order to maintain target haemoglobin (Hb) concentrations (11-13 g/dl). METHODS: Stable HD patients in routine clinical practice receiving i.v. darbepoetin alfa QW for a period of 6 months (n = 105) (treatment period 1) were switched to i.v. Q2W darbepoetin alfa for a further 6 months (treatment period 2) (n = 90). The dose of i.v. darbepoetin alfa was titrated to maintain Hb concentrations between 11 and 13 g/dl throughout the full 12-month study period. RESULTS: The mean change in Hb for treatment period 2 was 0.04 +/- 1.1 g/dl (+/-SD), which was not clinically relevant (11.7 +/- 0.8 g/dl vs 11.7 +/- 1.0 g/dl; P = 0.8). The mean weekly doses of darbepoetin alfa were similar throughout the treatment periods (34.0 +/- 17.1 microg/week vs 32.1 +/- 17.3 microg/week; P = 0.3, respectively for QW and Q2W dosing). Intravenous darbepoetin alfa was well tolerated. CONCLUSIONS: The treatment of renal anaemia in HD patients with i.v. Q2W darbepoetin alfa effectively and safely maintains Hb concentrations at a less frequent dosing regimen than observed with QW administration. Dose requirements for i.v. darbepoetin alfa administered QW or Q2W were not different. The results of this study demonstrate that i.v. darbepoetin alfa administered Q2W is an effective regimen for HD patients requiring anaemia treatment in routine clinical practice.     

Comparison of the therapeutic efficacy of epoetin beta and epoetin alfa in maintenance phase hemodialysis patients

In May 2009 for financial reasons, the epoetin product used for hemoglobin (Hb) maintenance in our renal dialysis unit was changed from epoetin beta to epoetin alfa. Although widely believed that the dosage requirements are the same, we undertook a retrospective analysis to investigate whether the dosage requirements in chronic renal failure patients were comparable for both preparations. We studied 128 stable end-stage renal failure patients on hemodialysis (three times per week) receiving erythropoietin therapy to maintain their Hb at 11-12.5 g/dL. Patients were excluded if within the study period they developed signs of infection, bleeding, required blood transfusion, were under-dialyzed, or required hospital admission. Regular monthly Hb concentrations and hematocrit (Hct) levels were measured for each patient. The weekly EPO index (defined as weekly epoetin dose/mean monthly Hct) was derived for each patient, before and after regime change. Of the 128 patients in end-stage renal failure, 79 were included in the study. There was no significant difference between the two preparations in terms of Hct level achieved (p = 0.15). However, the median weekly epoetin dose requirement increased from 6733 (range 750-30,000) IU/week to 9000 (250-30,667) IU/week (p < 0.001). EPO index similarly increased from 20,465 (2500-130,846) IU/week/% to 27,073 (729-98,937) IU/week/% (p < 0.001). Our study showed that a higher dose of epoetin alfa was needed to maintain target Hb concentration.     

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.     

A trial of subcutaneous administration of darbepoetin alfa once every other week for the treatment of anemia in peritoneal dialysis patients

BACKGROUND: Darbepoetin alfa (Aranesp, Amgen) is an erythropoietic stimulating protein with a three fold longer terminal half life than recombinant human erythropoietin (rHuEPO). The purpose of this single center, single arm study was to determine whether darbepoetin alfa is as effective as rHuEPO for the treatment of renal anemia in patients on peritoneal dialysis when administered at a reduced dosing frequency of once every other week irrespective of the initial rHuEPO dose frequency. METHODS: A total of 17 patients on peritoneal dialysis receiving stable rHuEPO therapy were changed to darbepoetin alfa every other week, using the recommended 200:1 conversion factor . The doses of darbepoetin alfa were titrated to maintain hemoglobin within -1.0 to +1.5 g/dL of the patients' baseline value and also within a range of 10.0 to 13.0 g/dL for up to 24 weeks (20 weeks dose titration period followed by 4 week evaluation period). The primary end point was change in hemoglobin levels between baseline and evaluation period. RESULTS: Mean change in hemoglobin levels from baseline to evaluation period was 0.03 g/dL (95% CI -0.62 to +0.69). This was not a statistically significant or clinically relevant difference, despite the reduced frequency of darbepoetin alfa administration. There were no serious or major adverse effects observed with darbepoetin alfa during the study. CONCLUSION: These results show that darbepoetin alfa maintains hemoglobin concentrations effectively and safely in patients on peritoneal dialysis, but with a reduced dose frequency as compared to rHuEPO.     

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.     

Fluctuations in haemoglobin levels in haemodialysis, pre-dialysis and peritoneal dialysis patients receiving epoetin alpha or darbepoetin alpha

Aim: To characterize the haemoglobin variability of haemodialysis, peritoneal dialysis and pre‐dialysis patients treated with either epoetin alpha or darbepoetin alpha in a clinical setting where treatment was administered according to current standard Australian practice. Methods: Data on haemodialysis, pre‐dialysis and peritoneal dialysis patients were extracted from the Renal Anaemia Management database (RAM) from 1 January 2001 to 31 December 2004. The variance in haemoglobin was calculated from patient records with more than five haemoglobin observations over a period of at least 4 weeks following 9 weeks of therapy. A mixed‐model was fitted to the within‐patient variances and weighting was based on the number of observations minus 1 for each record. Results: The mean within‐patient variance in haemoglobin levels for i.v. administered erythropoietin‐stimulating agents (IV) haemodialysis, s.c. administered erythropoietin‐stimulating agents (SC) haemodialysis, predialysis_SC and peritoneal dialysis_SC patients receiving epoetin alpha were 9% (95% CI: 13% to 5%, P < 0.0001), 17% (95% CI: 32% to 0.2%, P = 0.047), 19% (95% CI: 27% to 11%, P < 0.0001) and 26% (95% CI: 33% to 18%, P < 0.0001) lower than that for patients receiving darbepoetin alpha. The mean haemoglobin levels for haemodialysis_IV, haemodialysis_sc predialysis_SC and peritoneal dialysis_SC patients receiving darbepoetin alpha were 11.6 g/dL, 11.2 g/dL, 11.5 g/dL and 11.5 g/dL compared with 11.5 g/dL, 11.6 g/dL, 11.7 g/dL and 11.5 g/dL for patients receiving epoetin alpha. Conclusion: There was 9–26% greater within‐patient fluctuation in haemoglobin levels in patients receiving darbepoetin alpha compared with epoetin alpha. The causes of haemoglobin fluctuations and the implications for patient outcomes and resource use require further study.     

A comparison between epoetin omega and epoetin alfa in the correction of anemia in hemodialysis patients: a prospective, controlled crossover study

The objective of the study was to evaluate and compare the safety and effectiveness of epoetin omega (produced in baby hamster kidney cells) and epoetin alfa (produced in Chinese hamster ovary cells) in sustaining the correction of anemia in maintenance hemodialysis patients. The study, a prospective and controlled crossover, was completed in 38 stable patients treated with both epoetins for 24 weeks. Group A (17 patients) started with epoetin omega, and Group B (21 patients) started with epoetin alfa. After 24 weeks, a 4 week crossover (wash out) was made: Group A was switched to epoetin alfa and group B to epoetin omega for the next test period of 24 weeks. Both epoetins were administered subcutaneously after each dialysis. Doses were adjusted with the aim of maintaining a target hemoglobin level between 10 and 12 g/dl (hematocrit 30% to 35%). The mean weekly dose of epoetin omega/kg body weight (BW) was 67 +/- 43 U. The mean weekly dose of epoetin alfa/kg BW was 86 +/- 53 U. The average of all mean values of hemoglobin (Hb) during treatment with epoetin omega was 11.4 +/- 0.7 g/dl (hematocrit 34 +/- 2%), and during treatment with epoetin alfa was 11.3 +/- 0.7 g/dl (hematocrit 33 +/- 2%) (not significant). Thromboses of vascular access occurred in 3 patients during an epoetin omega treatment and in 3 patients during epoetin alfa treatment. At the site of injection, only 1 patient described a mild pain when treated with epoetin omega and only 6 patients when treated with epoetin alfa. In conclusion, both epoetin omega and epoetin alfa were effective in correcting the anemia of all studied patients. However, lower doses of epoetin omega were needed to maintain the same target hemoglobin level. No serious side effects with either epoetin were noted. The authors believe that additional comparisons of different epoetin preparations should be performed and will provide better insight into their biological activity and clinical responsiveness.     

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.     

Effects of haemoglobin normalization on quality of life and cardiovascular parameters in end-stage renal failure.

BACKGROUND: The optimal haemoglobin concentration ([Hb]) for patients with end-stage renal failure is uncertain. In particular, it is unclear whether Hb normalization may be an advantage to such patients who are otherwise well. METHODS: A prospective, randomized, double-blind cross-over study was completed in 14 haemodialysis patients (12 male) aged between 23 and 65 years over a period of 18 months, using a variety of measures to examine the effect of epoetin at target [Hb] of 10 g/dl ([Hb](10)) and 14 g/dl ([Hb](14)). Patients were randomized to maintain one or other of the target levels for 6 weeks before being crossed over to the alternative [Hb]. Baseline data (mean [Hb]: 8.5+/-0.2 g/dl) were also included selectively. Six patients were known to be hypertensive. Comparisons were made between 24-h ambulatory blood pressure levels (ABP), echocardiographic findings and estimates of blood volume (BV), plasma volume (PV) and Hb mass. Quality of life estimates were obtained using the Sickness Impact Profile (SIP), and epoetin dosage requirements at target [Hb] were assessed. RESULTS: Daytime and nocturnal ABP (systolic and diastolic) were not different at the respective target [Hb], although nocturnal diastolic levels were higher compared with baseline (73+/-4 mmHg) at both [Hb](10) (83+/-3, P:<0.01) and [Hb](14) (81+/-6, P:<0.05). Significant reductions in cardiac output (5.2+/-0.3 vs 6.6+/-0.5 l/min, P:<0.01) and left ventricular end-diastolic diameter (4.8+/-0.2 vs 5.2+/-0.2 cm, P:<0. 001) were found at [Hb](14) compared with [Hb](10). Left ventricular mass index was correlated with both PV (P:<0.001) and BV (P:<0.01), but not with Hb mass. The PV decreased as the [Hb] rose (P:<0.001) but BV remained unchanged. Quality of life was significantly improved at [Hb](14) compared with [Hb](10) for both total score (6. 5+/-1.7 vs 13.4+/-3.0, P:=0.01) and psychosocial dimension score (5. 4+/-1.9 vs 15.4+/-4.0, P:<0.01). The maintenance weekly dose of epoetin required was 80% higher at [Hb](14) compared with [Hb](10) (P:<0.001). CONCLUSION: These data suggest there may be a significant haemodynamic and symptomatic advantage in maintaining a physiological [Hb] in haemodialysis patients. Although untoward effects were not identified in this study at [Hb](14), a substantially higher dose of epoetin is required to maintain this level.     

Randomized trial on the therapeutic equivalence between Eprex and GerEPO in patients on haemodialysis

Aim: Treatment of renal anaemia with epoetin is well established. However, epoetin is expensive. Biogeneric epoetin with proven efficacy would reduce cost and improve access to therapy. We conducted this first ever comparative study of a biogeneric and the original product. Methods: Stable haemodialysis patients with haemoglobin (Hb) of at least 9 g/dL and receiving the human recombinant erythropoietin Eprex were randomized to continue Eprex or convert to GerEPO, a biogeneric epoetin, for 12 weeks. The primary efficacy variable was a change in Hb from baseline. Results: Ninety-three subjects were randomized to each arm. Ninety-two and 87 subjects on the Eprex and GerEPO arms, respectively, completed the trial. Mean Hb in both groups declined over time. The mean decline in Hb was -0.47 g/dL in the Eprex group and -0.45 g/dL in the GerEPO group. The mean difference in the change in Hb from baseline to week 12 between the two groups was 0.02. The 95% confidence interval was -0.42 to 0.46, which lies within the margin of equivalence (+/-0.5 g/dL). The results of intention-to-treat analysis were similar. There were no significant differences in the epoetin dose, iron therapy or iron stores between the groups. Patients receiving GerEPO reported more adverse events. Conclusion: GerEPO was therapeutically equivalent to Eprex with respect to Hb response for patients with Hb in the subtherapeutic target range as is common in this study population. The trial duration was insufficient for safety evaluation, which must await further investigation. More biogeneric products should be subjected to rigorous evaluation.     

Incidence of anaemia, and use of epoetin therapy in pre-dialysis patients: a prospective study in 403 patients.

BACKGROUND: Recent American and European guidelines recommend that epoetin therapy should be considered whenever the blood haemoglobin (Hb) level is <10-11 g/dl in dialysis patients and in pre-dialysis patients. Thus, data on the current prevalence of anaemia with respect to the degree of chronic renal insufficiency are needed in order to determine the potential indications of epoetin therapy in the pre-dialysis period. METHODS: We prospectively studied 403 consecutive ambulatory pre-dialysis patients whose serum creatinine (Scr) was 200 micro mol/l or more at their first passage at our out-patient clinic between January 1 and June 30, 1999. Hb and Scr values were determined at each visit until June 30, 2000, or until the start of maintenance dialysis. Patients had a clinical and laboratory evaluation every 2-3 months, and monthly when treated with epoetin. RESULTS: The mean (+/-SD) age of patients was 60.9+/-17.2 years at presentation. The Hb level was <11 g/dl in 62% of patients with Scr > or =400 micro mol/l, and in 58% of patients with an estimated creatinine clearance (Ccr) <20 ml/min/1.73 m(2). The proportion of anaemic patients was higher for any given Ccr value in females than in males. A total of 136 patients were treated with epoetin during the observation period. At the start of epoetin, their mean Hb value was 9.5+/-0.6 g/dl and Ccr level 13.9+/-4.9 ml/min/1.73 m(2). Among the 123 patients who began maintenance dialysis therapy during the observation period, 85 (or 69%) received epoetin therapy before the start of dialysis. Their mean Hb value at the start of dialysis was 10.8+/-1 g/dl compared with 10.5+/-1.1 g/dl in the 41 dialysed patients who did not require epoetin therapy during the pre-dialysis period. CONCLUSIONS: Based on the data gained in a large cohort of patients receiving regular pre-dialysis nephrological care, the proportion of subjects with a Hb level <11 g/dl may be estimated at approximately 60% when the Ccr is <20 ml/min/1.73 m(2). If the Hb level is to be maintained at no less than 11 g/dl, at least two-thirds of patients at this advanced stage of chronic renal failure should require pre-dialysis epoetin therapy.