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.     

Clinical and economic comparison of epoetin alfa and darbepoetin alfa

SUMMARY

Background: The pharmacoeconomics of erythropoietic therapy for the treatment of anemia is receiving renewed attention due to the current availability of two agents. Epoetin alfa has been the standard of therapy for patients with renal disease and cancer-related anemia for more than a decade. Darbepoetin alfa, an alternative agent, is now approved for anemia resulting from renal disease and cancer chemotherapy.

Methodology: Although direct comparative trials have not been performed with these agents, information published in the last several years regarding their clinical efficacy, safety, and dosing is sufficient, in most cases, to compare costs. With the disclaimer that any efficacy comparison of competing products using published reports has certain limitations, a cost-minimization approach from a provider's perspective was conducted.

Results:To provide background for the economic evaluation, pharmacokinetic and pharmacodynamic data for these two agents are discussed. Recent clinical trials in the nephrology and oncology therapeutic areas are summarized, highlighting study designs, dosing regimens, patient entry criteria, study endpoints, and published results. Cost data, based on average wholesale prices (AWP) in 2003, are compared and calculated from available clinical data with an emphasis on efficacy.

Conclusion: These evaluations largely conclude that epoetin alfa is the better pharmacoeconomic value of the two currently available erythropoietic agents.     

Clinical and economic comparison of epoetin alfa and darbepoetin alfa

BACKGROUND: The pharmacoeconomics of erythropoietic therapy for the treatment of anemia is receiving renewed attention due to the current availability of two agents. Epoetin alfa has been the standard of therapy for patients with renal disease and cancer-related anemia for more than a decade. Darbepoetin alfa, an alternative agent, is now approved for anemia resulting from renal disease and cancer chemotherapy. METHODOLOGY: Although direct comparative trials have not been performed with these agents, information published in the last several years regarding their clinical efficacy, safety, and dosing is sufficient, in most cases, to compare costs. With the disclaimer that any efficacy comparison of competing products using published reports has certain limitations, a cost-minimization approach from a provider's perspective was conducted. RESULTS: To provide background for the economic evaluation, pharmacokinetic and pharmacodynamic data for these two agents are discussed. Recent clinical trials in the nephrology and oncology therapeutic areas are summarized, highlighting study designs, dosing regimens, patient entry criteria, study endpoints, and published results. Cost data, based on average wholesale prices (AWP) in 2003, are compared and calculated from available clinical data with an emphasis on efficacy. CONCLUSION: These evaluations largely conclude that epoetin alfa is the better pharmacoeconomic value of the two currently available erythropoietic agents.     

The cost-effectiveness of weekly epoetin alfa relative to weekly darbepoetin alfa in patients with chemotherapy-induced anemia

OBJECTIVE: To compare the cost-effectiveness of epoetin alfa (EPO) and darbepoetin alfa (DARB) for the treatment of chemotherapy-induced anemia (CIA), using dosing regimens approved by the FDA (EPO 40,000 U once weekly and DARB 2.25 U once weekly and DARB 2.25 mcg/kg once weekly). METHODS: The study compared published results of two double-blind, randomized, phase III trials one utilizing EPO (N = 166) and the other, DARB (N = 367). Patients in both trials similar baseline characteristics. Effectiveness was measured as the proportion of EPO or DARB patients who were successfully treated (i.e., did not require blood transfusion) during weeks 0-16 and 5-16, respectively. Estimated drug costs were presented in 2005 USD based on wholesale acquisition cost (WAC) and average drug utilization over 16 weeks. Cost-effectiveness was calculated as the estimated drug costs divided by transfusion effectiveness. Threshold analysis was used to determine the break-even point at which EPO and DARB had the same drug costs. RESULTS: Estimated drug costs over 16 weeks were $9,039 for EPO and $13,555 for DARB. During weeks 5-16, 85% of EPO patients and 73% of DARB patients were successfully treated, resulting in average cost-effectiveness ratios of $106 for EPO and $186 for DARB per one per cent of successfully treated patients. A 33% reduction in DARB WAC was required to achieve the same drug costs as for EPO. CONCLUSIONS: Utilizing FDA-approved doses, EPO was found to result in lower drug costs and better treatment success when compared to DARB. Hence, EPO is a dominant alternative compared to DARB for the treatment of CIA. The analyses presented here are not without limitations. Specifically, although the studies were comparable, patients were ultimately drawn from different populations.     

Cost-minimization analysis of darbepoetin alfa versus epoetin alfa in the hospital setting.

PURPOSE: The cost of darbepoetin alfa versus that of epoetin alfa in a hospital setting was studied. METHODS: The study was an observational, retrospective review of the hospitalwide use of darbepoetin and epoetin during hospital admissions beginning in the period from January 2003 through April 2003. After the identification from daily charge reports of patients who used at least one of the study drugs during an admission, charts were requested for review. Drug product costs were determined from hospital purchasing information. Material and labor costs were combined to estimate drug administration costs. Total costs were calculated as the sum of drug product costs and administration costs. RESULTS: A total of 429 epoetin records and 80 darbepoetin records were included. The two cohorts were similar with respect to demographic characteristics. With respect to costs, the only significant difference between cohorts was in daily administration costs, which were lower for patients receiving darbepoetin. Sensitivity analysis found lower costs for darbepoetin only after the dose-conversion ratio (DCR) was increased to above 256.74 units:1 microg. The overall DCR based on the median daily dose of each drug was 244.90 units:1 microg. CONCLUSION: A cost-minimization study in a hospital showed no cost difference between treatment with epoetin and darbepoetin.     

The relative dosing of epoetin alfa and darbepoetin alfa in chronic kidney disease

ABSTRACT

Objective: The purpose of this study was to review and analyze current research to evaluate the dose ratio of epoetin alfa and darbepoetin alfa for the treatment of anemia in chronic kidney disease (CKD) and to identify determinants of the variation in epoetin alfa: darbepoetin alfa dose ratios across studies.

Methods: A systematic review of the literature for comparative switch and non-switch studies of epoetin alfa and darbepoetin alfa treatments in CKD for the period 2000–2005 was performed. Two reviewers independently assessed the quality of the information. Data on the study design and outcomes were collected for each selected study. The dose ratio from epoetin alfa to darbepoetin alfa was calculated for each study, and the results were reported stratified by study characteristics. To control for differences in study design and characteristics that could explain the variability in the relative dosages of the two agents across studies, multivariate regression analysis was conducted. Based on these results, a dose conversion ratio for Canada was estimated.

Results: A total of 21 studies involving 16?378 patients exposed to epoetin alfa or darbepoetin alfa in CKD were identified. Univariate analysis of the dose ratios indicated a mean dose ratio of 217:1 (IU of epoetin alfa:µg of darbepoetin alfa). Results from the multivariate analysis demonstrated that the study design (i.e., switch study versus straight comparison studies) and geographical coverage (i.e., United States) affected the results. Based on the multivariate analysis, the dose conversion ratio between epoetin alfa and darbepoetin alfa for Canada was 169:1.

Conclusions: Despite limitations associated with switching studies and the limited total number of studies available, this systematic review based on aggregated results provides further evidence to the clinical community that the dose conversion ratio for epoetin alfa:darbepoetin alfa in CKD patients in Canada is approximately 169:1. At that ratio, treatment with epoetin alfa is 11–18% cheaper than treatment with darbepoetin alfa in Canada.     

Chemotherapy-induced anemia: the story of darbepoetin alfa

Abstract

Background:

Prior to the approval of the first erythropoiesis-stimulating agent (ESA) in the early 1990s, red blood cell transfusions were the primary means of treating severe chemotherapy-induced anemia (CIA), with little recourse for those with more mild forms of the condition. The introduction of the ESAs allowed treatment of mild-to-moderate CIA in patients with cancer. It has been a decade since darbepoetin alfa (DA), a second-generation ESA with a longer half-life, became available to patients with CIA.     

Every-three-week administration of darbepoetin alfa in women with chemotherapy-associated anemia.

PURPOSE: The effectiveness of every-three-week administration of darbepoetin alfa in women with chemotherapy-associated anemia was evaluated. METHODS: Women receiving chemotherapy for gynecological tumors who had a hemoglobin concentration of <10 g/dL were recruited from an obstetrics and gynecology service. Study patients received subcutaneous darbepoetin alfa 6.75 microg/kg, followed by 4.5 microg/kg every three weeks for a total of up to six doses. Hematopoietic response and mean changes in hemoglobin concentrations were evaluated. The Functional Assessment in Cancer Therapy-Anemia (FACT-An) survey was self-administered before and after study completion to evaluate the patients' quality of life. RESULTS: The mean+/-S.D. age and weight for the 14 patients recruited (12 of whom were assessable) were 52.1+/-14 years and 64.6+/-19.8 kg, respectively. The mean initial and maintenance doses were 442 and 301.6 microg, respectively. The overall hematopoietic response was 64.3%, of which 35.7% were complete and 28.6% were partial. Peak response occurred at weeks 9 and 12. The mean+/-S.D. change in hemoglobin concentration was 1.6+/-1.51 g/dL. Treatment failure was predicted by week 9 (n=2). Maintenance doses were withheld if a patient's hemoglobin concentration exceeded 12 g/dL (n=3). The mean+/-S.D. point differential for FACT-An pretreatment and posttreatment scores was 5.8+/-4.71 (n=6). CONCLUSION: Every-three-week administration of subcutaneous darbepoetin alfa produced a complete or partial hematopoietic response in 11 of 14 women with chemotherapy- associated anemia. A quality-of-life indicator generally improved among the 6 patients for whom posttreatment quality-of-life data were available.     

Comparison of the therapeutic effects of epoetin zeta and epoetin alfa in the correction of renal anaemia

ABSTRACT

Objective: To assess the therapeutic equivalence of epoetin zeta and epoetin alfa for correction of haemoglobin (Hb) concentration in patients with anaemia and chronic kidney disease (CKD) stage 5 maintained on haemodialysis.

Study design: In total, 609 patients with CKD and anaemia (Hb?<?9?g/dL) were randomly assigned to receive either epoetin zeta or epoetin alfa intravenously, one to three times per week for 24 weeks. Dosing was titrated individually to achieve a stable, target Hb concentration of 11–12?g/dL. Primary endpoints were the mean weekly dose of epoetin per kilogram of body weight and mean Hb concentration during the last 4 weeks of treatment. Safety endpoints were the occurrence of anti-erythropoietin antibodies, ratings of tolerability and adverse events (AEs).

Results: Mean (± standard deviation [SD]) Hb concentration over the last 4 weeks of treatment was 11.61?±?1.27?g/dL for patients receiving epoetin zeta, compared with 11.63?±?1.37?g/dL for patients receiving epoetin alfa (95% confidence interval [CI]: –0.25 to 0.20?g/dL). Mean (± SD) epoetin zeta weekly dose over the last 4 weeks of treatment was 182.20?±?118.11?IU/kg/wk, compared with 166.14?±?109.85?IU/kg/wk for epoetin alfa (95% CI: –3.21 to 35.34?IU/kg/wk). The most commonly reported AEs (> 5% of patients) were infections and infestations (12.5% and 12.8% of patients treated with epoetin zeta and epoetin alfa, respectively) and vascular disorders (8.5% and 8.9%, respectively). No patients developed neutralizing anti-erythropoietin antibodies.

Conclusions: Epoetin zeta, administered intravenously, is therapeutically equivalent to epoetin alfa in the correction of low Hb concentration in patients with CKD undergoing haemodialysis. No unexpected AEs were seen and both epoetin zeta and epoetin alfa were well tolerated.     

Cost-minimization analysis of once-weekly versus thrice-weekly epoetin alfa for chemotherapy-related anemia

BACKGROUND: For individuals with chemotherapy-related anemia, the clinical effectiveness of epoetin alfa (EPO) dosed once weekly ([QW], 40,000 units per dose) has been demonstrated to be indistinguishable from that observed with thrice-weekly dosing ([TIW], 10,000 units per dose). Whether the advantage of less-frequent administration justifies the higher EPO dosage used in the weekly regimen in terms of overall cost of care is unknown. OBJECTIVE: To conduct a cost-minimization analysis comparing QW and TIW EPO dosing from a societal perspective. METHODS: Direct and indirect medical cost data were calculated for a 16-week period for 2 large, prospective, multicenter, community-based studies. Costs measured included EPO, transfusions, laboratory tests, office visits, and opportunity cost of patient time. RESULTS: The average total costs in 2002 (first half) dollars were nearly equivalent across the 2 groups (QW: 9,204 dollars; 95% confidence interval [CI], 9,057 dollars-9,350 dollars. TIW: 9,265 dollars; 95% CI, 9,083 dollars-9,447 dollars. P=0.60). QW incurred mean drug acquisition costs that were 23% higher (QW: 6,725 dollars; 95% CI, 6,611 dollars-6,838 dollars. TIW: 5,474 dollars; 95% CI, 5,350 dollars-5,598 dollars. P<0.001). However, QW patients can avoid the resource use and time cost associated with 2 additional office visits incurred each week (QW: 592 dollars [583 dollars-600 dollars]; TIW: 1,709 dollars [1,678 dollars-1,740 dollars]; P<0.001). Transfusion and laboratory test costs were slightly higher in the TIW group (QW: 1,888 dollars [1,837 dollars-1,940 dollars]; TIW: 2,082 dollars [2,020 dollars-2,144 dollars]; P<0.001). CONCLUSION: Total anemia treatment costs over a 16-week period with EPO QW were similar to those of TIW dosing. In the absence of cost differences between regimens, the noneconomic advantages of less-frequent dosing intervals should make weekly dosing increasingly attractive to patients, clinicians, and payers.     

Drug safety profile of darbepoetin alfa for anemia of chronic kidney disease

Anemia of chronic kidney disease due to deficiency of erythropoietin is common and has clinical consequences. Erythropoiesis stimulating agents including darbepoetin alfa (DA) are effective in correcting anemia. DA is generally well tolerated and has side effect profile similar to recombinant human erythropoietin. It has a long half-life permitting infrequent dosing. DA has been tested extensively in preclinical and clinical studies and significant experience has accumulated in clinical practice. Global safety profile of DA must consider recent data indicating worse survival, poor cardiovascular outcomes and thrombotic risks of targeting near normal hemoglobin levels and administering high doses of erythropoiesis stimulating agents. Strategies to achieve and maintain a reasonable, individualized target hemoglobin level with minimal variations in hemoglobin level are needed.