Once-monthly administration of darbepoetin alfa for the treatment of patients with chronic heart failure and anemia: a pharmacokinetic and pharmacodynamic investigation

In patients with chronic heart failure (CHF), anemia is associated with more severe symptoms and worse prognosis. Erythropoiesis-stimulating proteins (ESPs) increase hemoglobin and may be of therapeutic benefit. We investigated the pharmacokinetics and pharmacodynamics of the long-acting ESP, darbepoetin alfa, administered on 2 occasions 1 month apart to 30 healthy subjects and 33 patients with symptomatic CHF and anemia (hemoglobin相似文献   

Development and evaluation of a population pharmacokinetic-pharmacodynamic model of darbepoetin alfa in patients with nonmyeloid malignancies undergoing multicycle chemotherapy

Anemia is frequently observed in patients undergoing chemotherapy. Administration of darbepoetin alfa, a recombinant erythropoiesis-stimulating agent that has longer residence time than endogenous erythropoietin, to patients with chemotherapy-induced anemia (CIA) increases mean hemoglobin concentration, reduces risk of red blood cell transfusions, and improves patient-reported outcomes. A pharmacokinetic/pharmacodynamic (PkPd) model was developed using data from patients with nonmyeloid malignancies and CIA who were receiving darbepoetin alfa. A 2-compartment Pk model with linear elimination described the Pk data obtained in 140 CIA patients after intravenous and subcutaneous (s.c.) doses of 2.25 microg/kg every week and s.c. doses of 6.75 microg/kg every 3 weeks. The population typical values of key Pk parameters were clearance, 2010 mL/day; steady-state volume of distribution, 3390 mL; and bioavailability, 44.3%. A modified indirect response model, wherein serum concentrations stimulated the production of hemoglobin through an Emax-type equation, described the hemoglobin levels after s.c. doses of 0.5 microg/kg every week to 15 microg/kg every 3 weeks in 573 CIA patients. The estimated incremental maximum stimulation of hemoglobin production was 43.7% and darbepoetin alfa serum concentration at half-maximal stimulation was 3.68 ng/mL. The impact of covariates (body weight and platinum-containing chemotherapy) on the PkPd response was evaluated based on point and interval estimates of parameters, rather than through stepwise hypothesis testing. The final PkPd model adequately predicted hemoglobin response in a test data set, thereby confirming the predictive capability of the model. Based on simulations, it was not possible to categorize the influence of any covariate as clinically important.     

Reengineering clinical operations in a medical practice to optimize the management of anemia of chronic kidney disease

OBJECTIVES: To describe the clinic design, clinical evaluations, and treatment approaches used in a multidisciplinary clinic for management of anemia of chronic kidney disease (CKD), and to evaluate several selected clinical outcomes associated with this approach to anemia management. SETTING: University-affiliated, division of nephrology, outpatient multidisciplinary model CKD clinic headed by a clinical pharmacist. PATIENTS: One hundred sixty-six patients with anemia of CKD who were referred by nephrologists and primary care providers to the multidisciplinary clinic from March 1, 2002-July 31, 2004. MEASUREMENTS AND MAIN RESULTS: Patients received darbepoetin alfa dosed on an every-other-week basis. If patients were already receiving once-weekly recombinant human erythropoietin (r-HuEPO), the darbepoetin alfa dose was calculated by using the darbepoetin alfa package insert conversion table. If patients were na?ve to previous erythropoietic therapy, the darbepoetin alfa dose was either 60 microg or 0.7 microg/kg. The dose and frequency of darbepoetin alfa and oral iron supplements were adjusted to achieve the National Kidney Foundation Kidney Disease Outcomes Quality Initiative (K/DOQI) targets for hemoglobin levels and iron measures. The primary outcome analyzed was the proportion of patients with at least 30 days of treatment who achieved a target hemoglobin level of 11.0 g/dl or greater. Of 128 patients who received at least 30 days of treatment, 100 (78%) attained the hemoglobin level (mean +/- SD 11.7 +/- 7 g/dl). Ninety-nine of 128 patients were originally na?ve to erythropoietic therapy; 77 (78%) of these 99 patients achieved the hemoglobin target in a mean +/- SD of 7.9 +/- 7.5 weeks. These data contrast with the data of 29 patients seen in the year previous to the reengineered clinic process, whereby only 12 (41%) of these comparable patients reached hemoglobin target with r-HuEPO therapy. Of the 77 previously erythropoietic-na?ve patients, 82% were receiving darbepoetin alfa every other week, 14% every 3 weeks, and 4% every 4 weeks at the time the hemoglobin target was achieved. Oral iron administration significantly increased the chance of achieving the K/DOQI targets for hemoglobin and iron. CONCLUSION: Redefining roles and practices of members of a clinical practice and reengineering processes for anemia management were effective in achieving and maintaining target hemoglobin and iron levels.     

Pharmacokinetics of darbepoetin alfa after intravenous or subcutaneous administration in patients with non-myeloid malignancies undergoing chemotherapy

BACKGROUND AND OBJECTIVE: The pharmacokinetics of darbepoetin alfa after intravenous (IV) administration in the oncology setting have not been previously reported. The objective of this study was to evaluate the pharmacokinetics of IV or subcutaneous (SC) darbepoetin alfa in patients with non-myeloid malignancies undergoing multicycle chemotherapy. METHODS: Fifty-six patients (haemoglobin 相似文献   

Darbepoetin alfa: a novel erythropoiesis-stimulating protein

Darbepoetin alfa is a novel erythropoiesis-stimulating protein developed for the treatment of anemia. It is a hyperglycosylated analog of recombinant human erythropoietin with the same mechanism of action as erythropoietin, but with a three-fold longer terminal half-life after intravenous administration than recombinant human erythropoietin and the native hormone both in animal models and in humans. Clinical studies in patients with chronic renal failure either receiving or not receiving dialysis have shown that darbepoetin alfa is equivalent to recombinant human erythropoietin in terms of increases in hemoglobin concentration, percentage of patients achieving target hemoglobin concentration and average time to reach target hemoglobin concentration, although darbepoetin alfa is administered less frequently (once weekly or every other week). Clinical trials in cancer patients either receiving or not receiving chemotherapy have demonstrated that darbepoetin alfa is safe and effective in alleviating anemia at dose intervals of once every 1, 2 or 3 weeks, and results suggest that it may achieve greater and more rapid responses than recombinant human erythropoietin in cancer patients. Furthermore, an improvement in health-related quality of life has been observed in association with anemia correction using darbepoetin alfa therapy in these patients. Darbepoetin alfa has been approved for intravenous and subcutaneous administration by the European Commission and the FDA for the treatment of anemia in patients with chronic renal failure. Additionally, this product was recently approved by the FDA for the treatment of anemia in patients with nonmyeloid malignancies where anemia is due to the effect of concomitantly administered chemotherapy. The recommended starting dose in chronic renal failure patients is 0.45 microg/kg once weekly for both intravenous and subcutaneous administration, with subsequent titration based on the hemoglobin concentration. In cancer patients, the recommended starting dose is 2.25 microg/kg once weekly by subcutaneous injection and subsequent titration. The adverse event profile of darbepoetin alfa is similar to that of recombinant human erythropoietin in both settings. There are no reports of antibody formation associated with darbepoetin alfa in chronic renal failure patients, and three cases of antibody formation, with neutralizing activity in one of the cases, have been reported in cancer patients. However, no cases of antibody-mediated pure red cell aplasia have been reported. The longer half-life of darbepoetin alfa, together with a similar efficacy and safety profile, confers the clinical advantage over recombinant human erythropoietin of allowing a less frequent dosing (once weekly or every other week versus one to three times weekly in renal patients), thus reducing health-care utilization and probably improving patient compliance.     

Early hemoglobin response and alternative metrics of efficacy with erythropoietic agents for chemotherapy-related anemia

OBJECTIVE: To examine associations between early hemoglobin response and alternative measures of efficacy following treatment with an erythropoietic agent for chemotherapy-related anemia. RESEARCH DESIGN AND METHODS: Preliminary data from an ongoing randomized, multicenter, 16-week, open-label clinical trial of epoetin alfa versus darbepoetin alfa were used to dichotomize patients based on attainment of early hemoglobin response (> or = 1 g/dL increase in hemoglobin level within 4 weeks of treatment initiation). Measures of efficacy were compared between patients with early hemoglobin response and those without. Sensitivity analyses were then performed to evaluate the impact of various methods for handling censored data and hemoglobin values following blood transfusion. MAIN OUTCOME MEASURES: Efficacy measures included: the proportion of patients with a > or = 1 g/dL increase in hemoglobin by 4 weeks or a > or = 2 g/dL increase by 8 weeks; mean hemoglobin levels at 4, 8, 12, and 16 weeks; area under the curve for change in hemoglobin level; proportion of patients who required a blood transfusion after 4 weeks; proportion of follow-up days on which patients had hemoglobin levels within the therapeutic range of 11 g/dL to 13 g/dL; and proportion of patients who never had a hemoglobin level within this range. RESULTS: A total of 274 patients were included (66.1% female, mean age 62.4), of whom 48.9% had an early hemoglobin response and 51.1% did not. Mean duration of follow-up was 10.1 +/- 5.05 weeks. All metrics indicated superior longer-term response among patients with early hemoglobin response compared to patients without early response. The findings were robust across sensitivity analyses. Although the analysis establishes a significant relationship between early hemoglobin response and alternative efficacy metrics, causality cannot be inferred. CONCLUSIONS: Early hemoglobin response is significantly associated with various metrics of clinical response to erythropoietic agents and is an appropriate measure for evaluating treatment effects.     

Preference for monthly darbepoetin alfa dosing in patients with chronic kidney disease not receiving dialysis

ABSTRACT

Objective: To determine patient preference for once-weekly Epoetin alfa versus once-monthly (QM) darbepoetin alfa in patients with chronic kidney disease (CKD) not receiving dialysis.

Methods: AMPS (Aranesp Monthly Preference Study) consisted of two studies of similar design, each with a 2-week screening/baseline period, a 20-week QM darbepoetin alfa dosing period, and an 8-week follow-up period. Patients aged ≥18 years had a nephrologist-reported diagnosis of CKD but were not receiving dialysis, and were required to have at least two hemoglobin levels within 10–12?g/dL and to have been receiving a stable dose (< 25% change) of once-weekly or once- every-other-weekly Epoetin alfa for at least 8 weeks. At week 21, patients could continue on QM darbepoetin alfa or revert back to their previous Epoetin alfa regimen. The primary analysis assessed patient preference at week 21 for QM darbepoetin alfa versus previous onceweekly Epoetin alfa.

Results: AMPS enrolled 442 patients: 54% were female, 67% were Caucasian, and mean (SD) age was 68.3 (13.5) years. At week 21, 346 patients remained on study. Of the patients converted from once-weekly Epoetin alfa, 86% (138/161) preferred darbepoetin alfa QM, and of all patients who expressed a preference, regardless of previous Epoetin alfa dosing frequency, 96% (305/319) preferred QM darbepoetin alfa. Mean (SD) hemoglobin at week 29 of the study was similar to mean hemoglobin at baseline (for those who completed the study and were receiving QM darbepoetin alfa at week 29: 11.2 [1.1]?g/dL at week 29 versus 11.4 [0.7]?g/dL at baseline). QM darbepoetin alfa was well tolerated.

Conclusion: These data show that the majority of study patients preferred QM darbepoetin alfa to more frequent Epoetin alfa, and that QM darbepoetin alfa maintained hemoglobin levels at week 29 and was well tolerated over the study period. The single-item questionnaire could be a potential limitation of this study and further investigation with a multi-question instrument may be helpful in confirming these results.     

Randomized,double-blind,placebo-controlled trial of every-3-week darbepoetin alfa 300 micrograms for treatment of chemotherapy-induced anemia

ABSTRACT

Objective: Darbepoetin alfa is effective in treating chemotherapy-induced anemia (CIA). Administration of subcutaneous darbepoetin alfa every 3 weeks (Q3W) could simplify treatment through synchronization with common Q3W chemotherapy regimens. We report results from a multicenter, randomized, double-blind, placebo-controlled, phase 3 trial evaluating the efficacy and safety of fixed-dose Q3W darbepoetin alfa in patients with a wide variety of tumor types who experienced CIA.

Research design and methods: Patients aged?≥?18 years with anemia (hemoglobin <11?g/dL) being treated for nonmyeloid malignancy were randomized 1:1 to receive darbepoetin alfa 300?μg (n?=?193) or placebo (n?=?193) subcutaneously Q3W from weeks 1 to 13 in this 16-week study. Doses could be adjusted per prespecified rules.

Main outcome measures: The primary endpoint was the proportion of patients who received ≥1 red blood cell (RBC) transfusion between week 5 and the end of the treatment period (EOTP). The study also analyzed the proportions of patients achieving a hemoglobin concentration ≥11?g/dL and subsequently maintaining hemoglobin levels above 11?g/dL, and the change in hemoglobin concentration over time.

Results: The proportion of patients requiring RBC transfusions between week 5 and EOTP was significantly lower in the darbepoetin alfa-treated group than in the placebo-treated group (24 vs. 41% of patients, a 16.3% difference, p?<?0.001). There were no differences between the two treatment arms in quality-of-life measures. Cardiovascular/thromboembolic adverse events were uncommon and were not associated with increases in hemoglobin levels. Study limitations suggest caution in the interpretation of these results: transfusions, the primary endpoint, were recommended but not required if hemoglobin concentrations were ≤8.0?g/dL, and protocol deviations (primarily dosing errors) occurred in approximately one-half of the patients in both treatment groups.

Conclusions: In this study, fixed-dose Q3W darbepoetin alfa appeared to be well-tolerated and effective for the treatment of CIA.

Trial registration: ClinicalTrials.gov identifier: NCT00110955.     

Utilization of darbepoetin alfa and epoetin alfa for chemotherapy-induced anemia.

PURPOSE: The patterns of use and effectiveness of therapy with darbepoetin alfa and epoetin alfa for chemotherapy-induced anemia (CIA) in hospital outpatient and community settings were evaluated. METHODS: Data were collected from medical charts at 65 oncology clinics in hospital outpatient and community settings for consecutive patients who received the first dose of either darbepoetin alfa or epoetin alfa between August 1, 2002, and February 15, 2003, and were to have had 12 weeks of follow-up data. RESULTS: Data from the charts of 3123 patients were abstracted. Of these patients, 2785 were treated with only one erythropoietic agent (1444 with darbepoetin alfa and 1341 with epoetin alfa) and were included in the analysis. The most common initial dosage of darbepoetin alfa was 200 microg every two weeks (61% of darbepoetin alfa recipients), and the most common initial dosage of epoetin alfa was 40,000 units weekly (72%). With these regimens, the dosage was escalated for 22% of darbepoetin alfa recipients and 23% of epoetin alfa recipients at a median of six weeks after the initial dose. The mean change from baseline in hemoglobin concentration after 12 weeks of therapy was similar for both groups, as was the percent of patients with red-blood-cell transfusions during treatment. CONCLUSION: The most common initial dosage of darbepoetin alfa for CIA was 200 microg every two weeks, and the most common initial dosage of epoetin alfa was 40,000 units weekly. At these dosages, the two agents appear to have similar clinical effectiveness.     

Evaluation of the US Oncology Network's recommended guidelines for therapeutic substitution with darbepoetin alfa 200 microg every 2 weeks in both naïve patients and patients switched from epoetin alfa

STUDY OBJECTIVE: To evaluate the efficacy of darbepoetin alfa 200 microg subcutaneously every 2 weeks after therapeutic substitution for epoetin alfa. DESIGN: Retrospective multicenter chart review. SETTING: Three US Oncology-affiliated outpatient sites. PATIENTS: Three hundred thirty anemic patients with nonmyeloid malignancies, of whom 174 had been treated previously with epoetin alfa (switched group) and 156 had not been treated recently with epoetin alfa (naive group). INTERVENTIONS: Therapeutic substitution with darbepoetin alfa was started according to the US Oncology Pharmacy and Therapeutics Committee's recommended dosing guidelines: anemic patients with cancer received a starting dosage of darbepoetin alfa 200 microg every 2 weeks regardless of whether or not they had previously received epoetin alfa. Hematologic and darbepoetin alfa usage data were abstracted from consecutive medical records dated from May 2002-March 2003. MEASUREMENTS AND MAIN RESULTS: Median exposure to darbepoetin alfa was 10 weeks (25th quartile 6 wks, 75th quartile 17 wks) and 10 weeks (25th quartile 5 wks, 75th quartile 18 wks) for the naive and switched groups, respectively. The week before the switch to darbepoetin alfa, the 174 patients receiving epoetin alfa were administered the following weekly doses: less than 40,000 U (9%), 40,000 U (50%), or 45,000-90,000 U (41%). Mean hemoglobin level increased from baseline (wk 0) in both the naive and switched groups. The proportion of patients receiving a red blood cell transfusion in the darbepoetin alfa treatment phase was low (15% in each group). No variation in transfusion rates was observed across weight categories in patients who received a fixed dosage of darbepoetin alfa. Darbepoetin alfa was well tolerated. A detailed usage algorithm was validated by these results and is being used in these three US Oncology-affiliated practices. CONCLUSION: A darbepoetin alfa starting dosage of 200 microg subcutaneously every 2 weeks administered according to US Oncology-recommended dosing guidelines is effective in treating chemotherapy-induced anemia in both epoetin alfa-naive patients and those switched from epoetin alfa.     

Darbepoetin alfa: in patients with chemotherapy-related anaemia

Darbepoetin alfa, novel erythropoiesis stimulating protein closely related to human erythropoietin, has been developed for the treatment of chemotherapy-related anaemia in patients with non-myeloid malignancies. In three 12-week, phase II studies in patients with cancer and chemotherapy-related anaemia, subcutaneous darbepoetin alfa, administered in once-weekly or 2-, 3- or 4-weekly regimens, dose-dependently increased the mean haemoglobin levels. In a randomised, double-blind, phase III study in 320 patients with lung cancer and chemotherapy-related anaemia, recipients of subcutaneous darbepoetin alfa 2.25 micro g/kg once weekly, received red blood cell (RBC) transfusion approximate, equals 2-fold less frequently than placebo recipients (p < 0.001). In the same study, patients receiving darbepoetin alfa also received fewer standard units of RBC for transfusion and had greater haematopoietic response rate than placebo recipients (both p < 0.001). Subcutaneous darbepoetin alfa 2.25 micro g/kg once weekly also reduced patient-reported fatigue (assessed by a quality-of-life questionnaire) [p = 0.019 vs placebo]. black triangle Darbepoetin alfa was generally well tolerated in clinical trials. The most frequent darbepoetin alfa-related adverse events were: body oedema, arthralgia and skin rash.     

Anemia treatment with Q2W darbepoetin alfa in patients with chronic kidney disease naïve to erythropoiesis-stimulating agents*

ABSTRACT

Objective: To evaluate the efficacy and safety of darbepoetin alfa dosed every-other-week (Q2W) to treat anemia in subjects with chronic kidney disease (CKD), not receiving dialysis, who were naïve to erythropoiesis-stimulating agent (ESA) therapy.

Research design and methods: This was an open-label, multicenter, single-arm study enrolling ESA-naïve CKD subjects with baseline hemoglobin (Hb)?<?11.0?g/dL. Q2W darbepoetin alfa treatment was initiated at a dose of 0.75?µg/kg and titrated to achieve and maintain Hb levels at 11.0–13.0?g/dL. Treatment was administered from week 1 to week 19.

Main outcome measures: The primary endpoint was the proportion of subjects who achieved Hb?≥?11?g/dL at any study visit, except in week 1. Hb levels, darbepoetin alfa dose, and safety were also assessed.

Results: Of the 128 subjects who received at least one dose of darbepoetin alfa and of the subjects who completed the study, 118 (92%) and 112 (97%), respectively, achieved a Hb?≥?11?g/dL in a median time of 5 weeks. Median darbepoetin alfa dose at week 1 and at the time of achieving a Hb?≥?11?g/dL were 60 and 80?µg, respectively. Darbepoetin alfa was well-tolerated, and short-term adverse events were consistent with those expected in CKD subjects.

Conclusions: This study demonstrates that de novo Q2W darbepoetin alfa was effective in correcting and maintaining Hb levels in ESA-naïve subjects with CKD who were not receiving dialysis. Study limitations, including lack of a control arm for the study and multiple race information for subjects, must be considered in interpreting the results.

Trial registration: ClinicalTrials.gov identifier: NCT00112008.     

Early hemoglobin response and alternative metrics of efficacy with erythropoietic agents for chemotherapy-related anemia

ABSTRACT

Objective: To examine associations between early hemoglobin response and alternative measures of efficacy following treatment with an erythropoietic agent for chemotherapy-related anemia.

Research design and methods: Preliminary data from an ongoing randomized, multicenter, 16‐week, open-label clinical trial of epoetin alfa versus darbepoetin alfa were used to dichotomize patients based on attainment of early hemoglobin response (≥ 1?g/dL increase in hemoglobin level within 4 weeks of treatment initiation). Measures of efficacy were compared between patients with early hemoglobin response and those without. Sensitivity analyses were then performed to evaluate the impact of various methods for handling censored data and hemoglobin values following blood transfusion.

Main outcome measures: Efficacy measures included: the proportion of patients with a ≥ 1?g/dL increase in hemoglobin by 4 weeks or a ≥ 2?g/dL increase by 8 weeks; mean hemoglobin levels at 4, 8, 12, and 16 weeks; area under the curve for change in hemoglobin level; proportion of patients who required a blood transfusion after 4 weeks; proportion of follow-up days on which patients had hemoglobin levels within the therapeutic range of 11?g/dL to 13?g/dL; and proportion of patients who never had a hemoglobin level within this range.

Results: A total of 274 patients were included (66.1% female, mean age 62.4), of whom 48.9% had an early hemoglobin response and 51.1% did not. Mean duration of follow-up was 10.1 ± 5.05 weeks. All metrics indicated superior longer-term response among patients with early hemoglobin response compared to patients without early response. The findings were robust across sensitivity analyses. Although the analysis establishes a significant relationship between early hemoglobin response and alternative efficacy metrics, causality cannot be inferred.

Conclusions: Early hemoglobin response is significantly associated with various metrics of clinical response to erythropoietic agents and is an appropriate measure for evaluating treatment effects.     

An extended terminal half-life for darbepoetin alfa: results from a single-dose pharmacokinetic study in patients with chronic kidney disease not receiving dialysis

BACKGROUND AND OBJECTIVE: Anaemia is a major and persistent manifestation of chronic kidney disease (CKD) caused by the deficient production of erythropoietin in the kidneys, the prevalence of which is proportional to the deterioration in kidney function. Darbepoetin alfa, an erythropoiesis-stimulating protein, exhibits a lower clearance and longer terminal half-life in serum than recombinant human erythropoietin, thereby allowing for a reduced dosing frequency. A recent study in patients with CKD, using a 4-week sampling period, suggested that the terminal half-life of darbepoetin alfa in serum is longer than that reported in previous studies, which were based on a 1-week sampling period. This study was conducted to characterise the pharmacokinetic profile of a single subcutaneous dose of darbepoetin alfa 1 microg/kg in patients with CKD, using a sampling duration of 4 weeks, which was hypothesised to allow better characterisation of the terminal half-life in serum. METHODS: Twenty patients with CKD not on dialysis, with a calculated glomerular filtration rate of 20-60 mL/min and who had not been treated with erythropoietic agents in the previous 12 weeks, were enrolled into this single-dose, open-label study. Patients received a single subcutaneous dose of darbepoetin alfa (Aranesp) 1 microg/kg on day 1, and blood samples were collected for pharmacokinetic analyses predose, 6 and 12 hours postdose and up to 28 days postdose. Seroreactivity sampling and further safety laboratory tests (clinical chemistry and urinalysis) were also performed. Patients were assessed for adverse events at each study visit. The primary endpoint was characterisation of the terminal half-life following a single subcutaneous dose of darbepoetin alfa 1 microg/kg. RESULTS: The mean terminal half-life in serum of darbepoetin alfa was determined to be 69.6 hours. Peak serum concentrations were reached in a median time of 36 hours postdose, and a mean apparent clearance of 3.51 mL/h/kg was comparable to that observed previously in this patient population. CONCLUSION: Based on an extended sampling schedule of 4 weeks, the terminal half-life of darbepoetin alfa was approximately 70 hours. This is longer than the 48.8 hours reported previously in patients with CKD on dialysis. These data suggest that the pharmacokinetic properties of darbepoetin alfa make this erythropoietic agent well suited to an extended dosing regimen.     

Darbepoetin alfa: an effective treatment with flexible and simplified dosing for anemia in patients with cancer

Anemia is common in patients with cancer or myelodysplastic syndrome. Erythropoietic therapy offers an effective way to manage anemia by increasing hemoglobin levels, decreasing transfusion requirements, and alleviating symptoms. We reviewed data showing the feasibility and effectiveness of treatment with the erythropoiesis-stimulating protein darbepoetin alfa at extended dosing intervals to treat anemia in patients with cancer receiving multicycle chemotherapy. We also explored the darbepoetin alfa's potential for treating anemia in patients with myelodysplastic syndrome. Data from clinical studies and drug therapy evaluations confirm that darbepoetin alfa administered weekly, every 2 weeks, and every 3 weeks corrects and maintains hemoglobin levels in patients with chemotherapy-induced anemia. In addition, the data demonstrate that both weight-based and fixed dosing with darbepoetin alfa are effective, and that early intervention to treat anemia has clinical benefits. Darbepoetin alfa also is an effective treatment for anemia in patients with cancer not receiving chemotherapy, at extended dosing intervals of at least 3 weeks. Extended dosing for anemia treatment can provide benefits for patients, caregivers, and clinicians because it reduces the number of clinic visits needed and permits synchronizing anemia treatment with chemotherapy cycles. Data from recent studies suggest that darbepoetin alfa is effective for treating anemia in patients with myelodysplastic syndrome; this potential use is being investigated further in ongoing studies. Thus, darbepoetin alfa is an attractive therapy option for patients with chemotherapy or cancer-induced anemia. It allows increased flexibility and simplified dosing and may offer some benefit in the treatment of anemia in patients with myelodysplastic syndrome.     

Dosing patterns, hematologic outcomes, and costs of erythropoietic agents in predialysis chronic kidney disease patients with anemia

OBJECTIVE: Few observational studies have evaluated the use of epoetin alfa (EPO) and darbepoetin alfa (DARB) in chronic kidney disease (CKD) patients with anemia. The objective of this study was to investigate dosing patterns, hematologic outcomes, and intervention costs with EPO and DARB in anemic CKD patients treated in an ambulatory care setting. METHODS: This was a multicenter, retrospective, chart review of predialysis CKD patients with anemia treated with EPO or DARB. Charts were sequentially selected from 435 EPO and 432 DARB patients naive to erythropoietic therapy and treated for > or = 24 weeks. Hemoglobin (Hb) levels, dates, and EPO/DARB doses were recorded. Drug costs using 2005 wholesale acquisition costs (WAC) and Federal Supply Schedule (FSS) pricing were based on the mean cumulative drug dose over the 24-week study period. RESULTS: A total of 393 EPO and 396 DARB charts met all criteria with predominantly male subjects (EPO: 94%; DARB: 96%). Mean baseline GFR and Hb levels were similar. Once-weekly and extended dosing (> or = Q2W) was common in both groups. At Weeks 4, 8, and 12 following initiation of therapy, a greater proportion of EPO than DARB patients reached target Hb levels (> or = 11 g/dL) (p < 0.0001); at Week 24, all patients reached target Hb levels. Mean 24-week cumulative doses were EPO 279 336 +/- 68 302 units and DARB 1084 +/- 246 microg. Drug cost was higher for DARB independent of pricing utilized (WAC: EPO = 3400 US dollars, DARB = 4726 US dollars; FSS: EPO = 1528 US dollars, DARB = 2379 US dollars). CONCLUSIONS: Extended dosing (Q2W) was common in EPO- and DARB-treated patients with CKD-related anemia, with EPO-treated patients experiencing a significantly greater hematologic response (at Weeks 4, 8, and 12). In addition, drug cost was 39-56% higher in the DARB group. The male predominance may limit generalizability, warranting further research in other populations.     

Methoxy polyethylene glycol-epoetin beta versus darbepoetin alfa for anemia in non-dialysis-dependent CKD: a systematic review

Background Anemia management in non-dialysis-dependent chronic kidney disease (CKD) patients is associated with cardiovascular and cost benefits, slows decline in renal function, and prevents mortality. Different reviews have focused on evaluating the safety and efficacy of methoxy polyethylene glycol-epoetin beta (MPG-EPO), a continuous erythropoietin receptor activator, in CKD patients regardless of dialysis dependency and others have studied this novel agent exclusively in CKD patients receiving dialysis. Aim of the review To evaluate the efficacy and tolerability of MPG-EPO compared with other erythropoiesis stimulating agents (in particular darbepoetin alfa) for the treatment of anemia in non-dialysis-dependent CKD patients. Methods A systematic review of original studies published mainly in MEDLINE, Cochrane Database, ScienceDirect, ProQuest, clinical trials registries, and Google Scholar was carried out to identify randomized controlled trials (RCTs) comparing MPG-EPO with other erythropoiesis stimulating agents or placebo among patients with anemia of CKD who were not yet receiving dialysis. Data were independently extracted by two reviewers using standardized data abstraction tool. Results Four trials involving 1,155 patients were included in the review. The changes in hemoglobin level from the baseline reported by the reviewed studies demonstrate that MPG-EPO was clinically non-inferior to darbepoetin alfa. In addition, the studies documented that MPG-EPO-treated patients experienced a lower rate of hemoglobin level above the target range of 12–13 g/dL than darbepoetin-treated patients. The proportion of patients requiring RBC transfusion was higher among patients who received darbepoetin alfa than those who received MPG-EPO. However, the time to hemoglobin response was longer with MPG-EPO than with darbepoetin. Finally, the incidences of serious adverse events were similar between the two therapeutic agents. Conclusion There are currently only few well-designed head-to-head RCTs investigating the efficacy and safety of MPG-EPO compared with other ESAs in non-dialysis-dependent patients. MPG-EPO therapy compared with darbepoetin alfa has demonstrated favorable effects of increasing and maintaining hemoglobin concentrations to recommended target levels. This mini-review is not conclusive due to limited number of studies. Therefore, the beneficial effects and tolerability of MPG-EPO among non-dialysis-dependent CKD patients should be further investigated, given the economic and clinical benefits of managing anemia in this population.