Administration Of Epoetin Alfa Research Articles

Assessing EPO stability in urine and comparing recombinant EPO detectability in matched urine, venous serum, and capillary serum following a controlled epoetin alfa administration.

The instability of erythropoietin receptor agonists (ERAs, i.e., EPO) in urine presents a challenge to their detectability in doping control samples; however, this issue is not often seen in blood (serum) samples. With the anti-doping field beginning to transition into alternative blood collection technologies, it is important to understand recombinant EPO (rEPO) detectability in serum samples collected from one such capillary collection device, the Tasso+ SST. Twelve individuals were administered a single, 40 IU/kg dose of rEPO (epoetin alfa, EPOGEN®). Following administration, matched urine, venous serum, and capillary serum samples were concurrently collected. Urine aliquots were subject to various storage times and temperatures mimicking shipping conditions of doping control urine samples to assess EPO stability, while other urine aliquots, venous serum, and capillary serum aliquots were frozen until analysis to understand rEPO detectability across all three matrices. EPO and rEPO instability was identified in urine collected from 8 of 12 participants, especially in aliquots stored at room temperature and 37°C. In some of these unstable samples, rEPO was still detectable, while in others, no recombinant nor endogenous EPO was detectable and would have resulted in negative sample reports. Analyzing the concurrently collected urine, venous, and capillary serum samples, rEPO detectability was identical across the three matrices. In most cases, rEPO was detectable for at least 168 h post-administration. Noting greater stability in blood compared with urine, it is recommended that anti-doping authorities utilize this novel capillary serum collection technology to improve overall ERA detectability in doping control samples.

Efficacy and safety of darbepoetin alfa injection replacing epoetin alfa injection for the treatment of renal anemia in Chinese hemodialysis patients: A randomized, open-label, parallel-group, noninferiority phase III trial.

BackgroundThis study was to explore the clinical efficacy and safety of darbepoetin alfa injection replacing epoetin alfa injection (recombinant human erythropoietin injection, rHuEPO) for the treatment of anemia associated with chronic kidney failure in Chinese patients undergoing hemodialysis.MethodThis study was a multicenter, randomized, open‐label, intergroup parallel control phase III noninferiority trial from April 19, 2013 to September 9, 2014 at 25 sites. In this study, the members of the darbepoetin alfa group underwent intravenous administration once per week or once every two weeks. The members of the control drug epoetin alfa group underwent intravenous administration two or three times per week. All subjects underwent epoetin alfa administration during the 8‐week baseline period. After that, subjects were randomly assigned to the darbepoetin alfa group or epoetin alfa group. The noninferiority in the changes of the average Hb concentrations from the baseline to the end of the evaluation period (noninferiority threshold: −1.0 g/dl) was tested between the two treatments. The time‐dependent hemoglobin (Hb) concentration and the maintenance rate of the target Hb concentration (the proportion of subjects with Hb concentrations between 10.0 and 12.0 g/dl) were also evaluated. Iron metabolism, including changes in the serum iron, total iron‐binding capacity, ferritin, transferrin saturation, and comparisons of the dose adjustments between the two groups during the treatment period were analyzed further. Adverse events (AEs) were also observed and compared, and the safety was analyzed between the two treatment groups. The conversion rate switching from epoetin alfa to darbepoetin alfa was also discussed. SAS® software version 9.2 was used to perform all statistical analyses. Descriptive statistics were used for all efficacy, safety, and demographic variable analyses, including for the primary efficacy indicators.ResultsFour hundred and sixty‐six patients were enrolled in this study, and ultimately 384 cases were analyzed for safety, including 267 cases in the darbepoetin alfa group and 117 cases in the epoetin alfa group. There were 211 cases in the per‐protocol set, including 152 cases in the darbepoetin alfa group and 59 cases in the epoetin alfa group. The changes in the average Hb concentrations from the baseline to the end of the evaluation period were −0.07 and −0.15 g/dl in the darbepoetin alfa group and epoetin alfa group respectively. The difference between the two groups was 0.08 g/dl (95% confidence interval [CI]: −0.22 to 0.39), and the lower limit of the 95% CI was −0.22 > −1.0 g/dl. The average Hb concentrations of the two groups were 10.88–11.43 g/dl (darbepoetin alfa) and 10.91–11.38 g/dl (epoetin alfa) during the study period of Weeks 0–28, with the maintenance rates of the target Hb concentration ranging within 71%–87% and 78%–95% in the darbepoetin alfa group and epoetin alfa group respectively. During the period of comparison between the two groups, the incidence of AEs in the darbepoetin alfa group was 61.42%, while in the epoetin alfa group it was 56.41%. All of the adverse events and reactions in the study were those commonly associated with hemodialysis.ConclusionThe overall efficacy and safety of darbepoetin alfa for the treatment of Chinese renal anemia patients undergoing hemodialysis are consistent with those of epoetin alfa.

P1383ECONOMIC BENEFITS OF SWITCHING FROM INTRAVENOUS TO SUBCUTANEOUS ERTHROPOIESIS-SIMULATING AGENTS THERAPY FOR MANAGEMENT OF ANEMIA IN HEMODIALYSIS PATIENTS

Abstract Background and Aims Erythropoiesis stimulating agents (ESA’s) were introduced in the treatment of anemia in 1989 and it immediately led to a marked decline in the number of blood transfusions and improved quality of life in patients across the spectrum of chronic kidney disease. Several studies from the mid 1990s have shown that the required doses of Epoetin alpha were lower when administered subcutaneously (SQ). These studies led to guidelines by NKF (1997) and KDOQI (2001) recommending the use of SQ over intravenous (IV) as considerable cost savings could be achieved without compromising care. The rise in the reported cases of pure red cell aplasia (PRCA) led to a change in guidelines in 2006 and led to units changing exclusively to IV route. It was subsequently identified that polysorbate 80 from uncoated rubber stoppers in pre-filled syringes rather than the route of administration was the most plausible cause of PRCA. However, higher doses of ESAs, have been associated with adverse health outcomes across all hematocrit categories in hemodialysis patients. While the current practice is to administer ESAs to patients through IV route, SQ ESAs achieve the same target hemoglobin level at a reduced dose and cost. Given the dose -sparing advantages of SQ Epoetin alpha administration, we decided to gradually transition our patients to SQ and examined the cost of IV versus SQ treatment. The objective of our study was to determine the economic benefit of the change in the route of administration from IV to SQ ESA in hemodialysis patients. Method We conducted a retrospective cohort study in 215 hemodialysis patients who transitioned from IV Epoetin alfa to SQ at four hemodialysis sites in the province of Saskatchewan, Canada from September 2014 to July 2017. The dose and cost of different routes of Epoetin alfa administration per patient per month was calculated. Also, blood hemoglobin, markers of erythropoiesis (transferrin saturation and Ferritin), IV iron dose and cost were determined in relation to route of Epoetin alfa administration. The dependent t-test was used to compare mean variables between pre-switch and post-switch period. Differences in variables across three serum hemoglobin ranges (<95, 95-115, >115 gram/liter) were assessed using the independent t-test. Results The mean Epoetin alfa doses per patient per month (47,327.9±33,133.0 international unit) during pre-switch (IV) period were greater than of post-switch (SQ) period (34,253±24,858.1), a decrease of 27.62% (p<0.001). The mean hemoglobin concentration for patients in both periods remained stable (103.3±9.2 versus 104.3±13.3, p=0.34) and within the target range. The reduction in the dose of Epoetin alfa per patient per month (IU± standard deviation) upon conversion remained similar (IV versus SQ) in all the subcategories: hemoglobin <95 g/L (65,941 versus 52,717), hemoglobin 95-115g/L (42,120 versus 29,619) and (35,289 versus 17,651) for hemoglobin >115 g/L. There were no significant differences in transferrin saturation, Ferritin and IV iron dose and cost between the two study periods. The mean cost (CAD± SD) of Epoetin alfa per patient per month decreased from 674.4±477.4 pre-switch to 484.8±354.3 post-switch (p<0.001), a decrease of 28.11%; whereas, the cost of IV iron remained similar in pre- and post-switch period. Conclusion The (mean) cost of Epoetin alfa per patient per year in our study when given IV was $ 8,088 (CAD) and once converted to SQ was $ 5,817 (CAD) while achieving equivalent hemoglobin levels, a saving of $ 2271 (CAD) per year. Based on these values, if we extrapolate our savings to 900 prevalent patients to SQ Epoetin alfa we can realize a cost saving of $2,043,900 per year. Conversion of Epoetin alfa from IV to SQ led to substantial cost savings at our hemodialysis units.

Economic Benefits of Switching From Intravenous to Subcutaneous Epoetin Alfa for the Management of Anemia in Hemodialysis Patients.

Background:Erythropoiesis-stimulating agents including epoetin alfa have been a mainstay of anemia management in patients with chronic kidney disease. Although the standard practice has been to administer epoetin alfa to patients on hemodialysis (HD) intravenously (IV), subcutaneous (SQ) epoetin alfa is longer acting and achieve the same target hemoglobin level to be maintained at a reduced dose and cost.Objective:The primary objective of this study was to determine the economic benefits of change in route of epoetin alfa administration from IV to SQ in HD patients. The secondary objectives were (1) to determine the differences in epoetin alfa doses at the pre-switch (IV) and post-switch period (SQ) and (2) to determine serum hemoglobin concentration, transferrin saturation, ferritin level, IV iron dose and cost in relationship to route of epoetin alfa administration.Design:This retrospective observational study included patients who transitioned from IV to SQ epoetin alfa.Setting:Two HD sites in southern Saskatchewan (Regina General Hospital, and Wascana Dialysis Unit, Regina) and 2 sites in northern Saskatchewan (St. Paul’s [SPH] Hospital, and SPH Community Renal Health Center, Saskatoon).Patients:The study includes 215 patients who transitioned from IV to SQ and were alive at the end of 12-month follow-up period.Measurements:We calculated the dose and cost of different routes of epoetin alfa administration/patient month. Also, serum hemoglobin, markers of iron stores (transferrin saturation and ferritin), IV iron dose, and cost were determined in relation to route of epoetin alfa administration.Methods:Data were gathered from 6 months prior (IV) to 12 months after switching treatment to SQ. The paired t-test and Wilcoxon signed-rank test were used to compare variables between pre-switch (IV) and post-switch (SQ) period.Results:The median cost (interquartile range) of epoetin alfa/patient-month decreased from (CAD508.3 [CAD349-CAD900.8]) pre-switch (IV) to (CAD381.2 [CAD247-CAD681]) post-switch (SQ) (P < .001), a decrease of 25%. The median epoetin alfa dose/patient-month reduced from (38 500 [25 714.3-64 166.5] international unit) pre-switch to (26 750.3 [17 362.6-48 066] IU) post-switch (P < .001), a decrease of 30.51%. The mean hemoglobin concentration (± standard deviation) for patients in both periods remained stable (103.3 ± 9.2 vs 104.3 ± 13.3 g/L, P = .34) and within the target range. There were no significant differences in transferrin saturation, ferritin, and IV iron dose and cost between the 2 study periods.Limitations:We were unable to consistently obtain information across all the sites on hospitalizations, inflammatory markers, nutritional status, and gastrointestinal bleeding. In addition, as our study sample was subject to survival bias, we cannot generalize our study results to other populations.Conclusions:We have shown that administering epoetin alfa SQ in HD patients led to a 30.51% reduction in dose and 25% reduction in cost while achieving equivalent hemoglobin levels. Given the cost sparing advantages without compromising care while achieving comparable hemoglobin levels, HD units should consider converting to SQ mode of administration.Trial registration:The study was not registered on a publicly accessible registry as it was a retrospective chart review and exempted from review by the Research Ethics Board of the former Regina Qu’Appelle Health Region.

Time spent on erythropoietin stimulating agents administration in hemodialysis centers in Panama: a time and motion study

Objectives: There is a lack of data in Panama on the potential differences in total healthcare professional (HCP) time between routine administrations of short-acting erythropoietin simulating agents (ESAs) (i.e. epoetin alfa) and continuous erythropoietin receptor activator (CERA) (i.e. methoxy polyethylene glycol–epoetin beta). This study aimed to quantify the HCP time associated with a single administration of epoetin alfa and CERA for the treatment of anemic patients with chronic kidney disease (CKD) on hemodialysis. Methods: This was a multi-center, cross-sectional study, using a time-and-motion methodology. Costs related to HCP time and consumables usage associated with administration of epoetin alfa and CERA were estimated. Results: Based on 60 administrations of either CERA or epoetin alfa, the estimated savings in mean total active HCP time were 2.34 (95% confidence interval = 1.87–2.81) min (–30%) per administration. When extrapolating to a full year’s treatment with intravenous ESA, it would require a total of 20.3 (95% CI = 19.90–20.71) h of HCP time for epoetin alfa vs 1.1 (95% CI = 1.01–1.19) h for CERA per patient per year. Estimated savings in active HCP time per patient per year were 19.20 (95% CI = 19.20–19.21) h (–95%). This, in turn, translates into staff cost efficiency that favors Mircera with an estimated annual saving of $78.24 (95% CI = 78.24–78.28) (–95%) per patient. Conclusions: Data from a real-world setting showed that the adoption of CERA could potentially lead to a reduction in active HCP time. Highlights Few comparative data have explored the costs and potential savings of using long-acting erythropoietin–stimulating agents (ESA) instead of short-acting ESAs to treat anemia in CKD patients on hemodialysis. This time-and-motion study shows that use of CERA reduces total healthcare professional time and could represent a save for an institution in a real-world setting in Panama.

Time savings of weekly versus three-times-per-week administration of erythropoiesis stimulating agents in United States dialysis patients

Objective:Previous research suggests that erythropoiesis stimulating agent (ESA) administration in dialysis is a time-consuming task and switching to less frequently dosed ESAs may offer operational efficiencies. Our objective was to describe and measure the time spent on tasks in the ESA administration process in US dialysis centers, and to estimate potential efficiency gains of using weekly (QW) administration vs three-times-per-week (TIW) administration.Methods:We conducted a time and motion study of staff time required to prepare, administer and document ESA doses. Dialysis centers using intravenous administration of TIW epoetin alfa (EPO) or QW darbepoetin alfa (DPO) were selected in pairs (one EPO, one DPO) from the same organization to help control for differences in ESA protocols and staffing patterns across organizations. ESA-related tasks were timed by trained observers. Time savings of TIW vs QW administration were estimated. Staff were interviewed about alternate activities that could be accomplished if time were saved in the ESA process.Results:A total of 200 administrations were observed (81 DPO, 119 EPO). A mean of 2.26 (95% CI: 2.1–2.5) minutes per dose were required for ESA administration. ESA process time per administration did not vary significantly between EPO and DPO (p = 0.83). Estimated potential monthly staff time savings for an average facility of 70 patients totaled 23 hours, due to fewer ESA administrations using QW DPO. Patient education and fulfillment of care plans were identified as opportunities for improved care processes that could be implemented if staff time was freed up from the ESA process.Limitations:Results should not be generalized to other countries, ESAs and/or dosing frequencies.Conclusions:Switching from TIW EPO to QW DPO can result in time savings due to fewer administrations and provide opportunities to redirect nurse time towards activities aimed at improving patient care.

Relative safety of peginesatide and epoetin alfa.

Peginesatide, a long-acting erythropoiesis-stimulating agent, was recalled in February 2013 following reports of serious and sometimes fatal hypersensitivity reactions in dialysis patients who received a first dose. We assessed the relative risks of mortality and morbidity in peginesatide-treated and matched epoetin alfa-treated patients. From standardized extracts of paid Medicare claims in 2012 and 2013, we identified dialysis patients treated with peginesatide or epoetin between 1 July 2012 and 28 February 2013. For each peginesatide-treated patient, we identified with propensity score matching two epoetin-treated control patients. Patients were followed for up to 2 days after the first peginesatide dose or the referent epoetin dose for death or hospitalization as a result of cardiovascular morbidity or symptoms (composite event), all-cause hospitalization, and emergency room care. We identified 15 633 peginesatide-treated patients and 31 266 matched epoetin-treated controls. On the day of dose administration, 19 composite events occurred with peginesatide (incidence, 0.12%) and 14 with epoetin (0.04%); the hazard ratio was 2.7 (95% confidence interval, 1.4-5.4). With follow-up for 1 and 2 subsequent days, hazard ratios were 1.6 (1.0-2.4) and 1.5 (1.1-2.0), respectively. Corresponding hazard ratios were larger among hemodialysis patients with neither intravenous antibiotic nor intravenous iron exposure on the day of dose administration. Hazard ratios for all-cause hospitalization and emergency room care exceeded 1 on and after the day of dose administration. Relative to administration of epoetin alfa, first administration of peginesatide in dialysis patients was acutely associated with higher risk of death or hospitalization as a result of cardiovascular morbidity or symptoms.

Long Term Effects of Epoetin Alfa in Patients with ST- Elevation Myocardial Infarction

The HEBE III trial showed that epoetin alfa administration in patients with a first ST-elevation myocardial infarction (STEMI) did not improve left ventricular function at 6 weeks after primary percutaneous coronary intervention (PCI). The long term effects of erythropoiesis- stimulating agents on cardiovascular morbidity and mortality are unknown, therefore we evaluated clinical events at 1 year after PCI. A total of 529 patients with a first STEMI and successful primary PCI were randomized to standard optimal medical treatment (N = 266) or an additional bolus of 60,000 IU epoetin alfa administered intravenously (N = 263) within 3 h after PCI. Analyses were performed by intention to treat. At 1 year after STEMI, 485 patients had complete follow-up. The rate of the composite end point of all-cause mortality, re-infarction, target vessel revascularization, stroke and/or heart failure was 6.4 % (N = 15) in the epoetin alfa group and 9.6 % (N = 24) in the control group (p = 0.18). Thromboembolic events were present in 1.3 % (N = 3) of patients in the epoetin alfa group and 2.4 % (N = 6) in the control group. There was no evidence of benefit from epoetin alfa administration in subgroups of patients. Administration of a single bolus of epoetin alfa in patients with STEMI does not result in a reduction of cardiovascular events at 1 year after primary PCI. There was a comparable incidence of thromboembolic complications in both treatment groups, suggesting that epoetin alfa administration is safe at long term.

Impact of Epoetin Alfa on Left Ventricular Structure, Function, and Pressure Volume Relations as Assessed by Cardiac Magnetic Resonance: The Heart Failure Preserved Ejection Fraction (HFPEF) Anemia Trial

Anemia, a common comorbidity in older adults with heart failure and a preserved ejection fraction (HFPEF), is associated with worse outcomes. The authors quantified the effect of anemia treatment on left ventricular (LV) structure and function as measured by cardiac magnetic resonance (CMR) imaging. A prospective, randomized single-blind clinical trial (NCT NCT00286182) comparing the safety and efficacy of epoetin alfa vs placebo for 24 weeks in which a subgroup (n=22) had cardiac magnetic resonance imaging (MRI) at baseline and after 3 and 6 months to evaluate changes in cardiac structure and function. Pressure volume (PV) indices were derived from MRI measures of ventricular volume coupled with sphygmomanometer-measured pressure and Doppler estimates of filling pressure. The end-systolic and end-diastolic PV relations and the area between them as a function of end-diastolic pressure, the isovolumic PV area (PVAiso), were calculated. Patients (75±10 years, 64% women) with HFPEF (EF=63%±15%) with an average hemoglobin of 10.3±1.1 gm/dL were treated with epoetin alfa using a dose-adjusted algorithm that increased hemoglobin compared with placebo (P<.0001). As compared with baseline, there were no significant changes in end-diastolic (-7±8 mL vs -3±8 mL, P=.81) or end-systolic (-0.4±2 mL vs -0.7±5 mL, P=.96) volumes at 6-month follow-up between epoetin alfa compared with placebo. LV function as measured based on EF (-1.5%±1.6% vs -2.6%±3.3%, P=.91) and pressure volume indices (PVAiso-EDP at 30 mm Hg, -5071±4308 vs -1662±4140, P=.58) did not differ between epoetin alfa and placebo. Administration of epoetin alfa to older adult patients with HFPEF resulted in a significant increase in hemoglobin, without evident change in LV structure, function, or pressure volume relationships as measured quantitatively using CMR imaging.

Treating Anemia in Older Adults With Heart Failure With a Preserved Ejection Fraction With Epoetin Alfa

Background— Anemia is a common comorbidity in older adults with heart failure and a preserved ejection fraction and is associated with worse outcomes. We hypothesized that treating anemia with subcutaneous epoetin alfa would be associated with reverse ventricular remodeling and improved exercise capacity and health status compared with placebo. Methods and Results— Prospective, randomized, single-blind, 24-week study with blinded end point assessment among anemic (average hemoglobin of 10.4±1 g/dL) older adult patients (n=56; 77±11 years; 68% women) with heart failure and a preserved ejection fraction (ejection fraction=63±15%; B-type natriuretic peptide=431±366 pg/mL) was conducted. Treatment with epoetin alfa resulted in significant increases in hemoglobin ( P &lt;0.0001). Changes in end-diastolic volume (−6±14 versus −4±16 mL; P =0.67) at 6 months did not differ between epoetin alfa and placebo, but declines in stroke volume (−5±8 versus 2±10 mL; P =0.09) without significant changes in left ventricular mass were observed. Changes in 6-minute walk distance (16±11 versus 5±12 m; P =0.52) did not differ. Although quality of life improved by the Kansas City Cardiomyopathy Questionnaire and the Minnesota Living with Heart Failure Questionnaire in both cohorts, there were no significant differences between groups. Conclusions— Administration of epoetin alfa to older adult patients with heart failure and a preserved ejection fraction compared with placebo did not change left ventricular end-diastolic volume and left ventricular mass nor did it improve submaximal exercise capacity or quality of life. Clinical Trial Registration— URL: http://www.clinicaltrials.gov . Unique identifier: NCT00286182.

Desensitization to Epoetin Alfa in a Patient with Anaphylaxis: a Case Report

Epoetin alfa is a human recombinant erythropoietin widely used to treat anemia in patients with chronic kidney disease. Anaphylaxis to epoetin alfa has been described, but desensitization to epoetin alfa in the setting of IgE-mediated reaction has not been reported. We present a case of a hemodialysis patient with anemia associated with chronic kidney disease that developed symptoms of anaphylaxis (generalized pruritus, urticaria, oropharyngeal edema, and hypotension) after administration of epoetin alfa and eventually tolerated desensitization to the medication.

A randomized, double-blind, placebo-controlled study to assess the effect of recombinant human erythropoietin on functional outcomes in anemic, critically ill, trauma subjects: the Long Term Trauma Outcomes Study

BackgroundAchieving a higher hemoglobin (Hb) level might allow the anemic, critically ill, trauma patient to have an improved outcome during rehabilitation therapy. MethodsPatients with major blunt trauma orthopedic injuries were administered epoetin alfa or placebo weekly both in hospital and for up to 12 weeks after discharge or until the Hb level was >12.0 g/dL, whichever occurred first. The 36-question Short Form Health Assessment questionnaire (SF-36) was used to evaluate physical function (PF) outcomes at baseline, at hospital discharge, and at several time points posthospital discharge. ResultsOne hundred ninety-two patients were enrolled (epoetin alfa [n = 97], placebo [n = 95]). Hb increased from baseline to hospital discharge in both groups (epoetin alfa: 1.2 g/dL vs placebo: 0.9 g/dL), and transfusion requirements were similar between groups. Both groups showed improvements in SF-36 PF; there were no significant differences in the average of all posthospital discharge scores (epoetin alfa: 27.3 vs placebo 30.9; P = 0.38). Thromboembolic events were similar between groups. ConclusionsNo differences were observed in physical function outcomes or safety in anemic, critically ill, trauma patients treated with epoetin alfa compared with placebo.

An Open-Label, Randomized, Multicenter, Controlled Study of Epoetin Alfa for the Treatment of Anemia of Chronic Kidney Disease in the Long Term Care Setting

To evaluate the safety and efficacy of epoetin alfa administered in extended-dosing intervals to a target hemoglobin (Hb) level not exceeding 12.0 g/dL for the treatment of anemia in subjects with chronic kidney disease (CKD) not on dialysis. An open-label, randomized, multicenter, controlled study consisting of a 1-week screening phase and a 26-week open-label treatment phase. Twenty-seven long term care (LTC) facilities in the United States. Subjects with CKD who were not receiving dialysis, who had not received an erythropoiesis-stimulating agent for 8 weeks before screening, and whose Hb levels were lower than 11.0 g/dL at screening were eligible. In the epoetin alfa group, subjects were administered 20,000 international units epoetin alfa subcutaneously every 2 weeks (Q2W). Dosing was based on the Hb concentration measurement obtained by HemoCue Hb201+System (Quest Diagnostics; Madison, NJ) at the time of the scheduled dose. When the Hb concentration was 11.0 to 11.5 g/dL on 2 consecutive biweekly measurements, the dose was doubled and administered on the day that the second consecutive measurement was obtained. The dosing interval was then extended to every 4 weeks (Q4W). Subjects in the standard of care (SOC) group received treatment for their anemia according to the practice of the LTC facility. Study visits were every 2 weeks, at which time blood was drawn and used for efficacy analysis. Measurements included: the Hb concentration change from baseline to the end of the study; the proportion of subjects who achieved an Hb response (defined as 2 consecutive Hb measurements at least 1.0 g/dL greater than baseline or 2 consecutive Hb measurements ≥11.0 g/dL at any time during the study); the time to the Hb response; the proportion of subjects who received a transfusion and the number of units of transfused; the proportion of epoetin alfa-treated subjects converting to Q4W dosing; and the proportion of subjects who converted to Q4W dosing and remained on Q4W dosing through the end of the study. A total of 157 subjects were randomized: 118 subjects to the epoetin alfa group and 39 to the SOC group. The mean change in Hb was significantly greater in the epoetin alfa group (0.9 g/dL) compared with the SOC group (0.3 g/dL) (P= .006). A significantly greater percentage of subjects achieved a Hb response in the epoetin alfa group (85.1%) compared with the SOC group (53.8%) (P < .001). The time to achieve a Hb response was significantly shorter in the epoetin alfa group (41 days) than in the SOC group (114 days) (P < .0001). There were no transfusions in the SOC group, whereas 4 subjects (3.5%) required transfusions in the epoetin alfa group. Of the 114 subjects receiving epoetin alfa, 33(28.9%) subjects were converted to Q4W dosing, and all subjects who converted were able to be maintained on this schedule. The administration of epoetin alfa in extended-dosing intervals of Q2W followed by Q4W was safe and effective in the treatment of anemia in subjects with CKD who reside in LTC facilities.

A randomized, open-label, multicenter study evaluating thrombovascular events (TVEs) in subjects with cancer receiving chemotherapy and administered epoetin alfa (EPO) once weekly (QW) or three times a week (TIW) for the treatment of anemia.

e19550 Background: Extensive clinical experience has demonstrated the safety and efficacy of EPO for treatment of chemotherapy- induced anemia. An increased incidence of TVEs is a known and labeled event in cancer patients receiving ESAs. This study compared the incidence of clinically relevant and objectively confirmed TVEs in the 2 approved dosing regimens (QW and TIW) of EPO when used per label instructions to treat anemia in subjects with nonmyeloid malignancies who are receiving chemotherapy. Methods: Eligible subjects (n = 504) were randomly assigned in a 1:1 ratio to receive EPO either TIW or QW. The sample size was estimated to provide at least 80% power (with 2 sided type I error of 0.05) to rule out an absolute difference of 6% in the TVE rates between the 2 groups assuming a TVE rate of approximately 6% in the TIW group. Randomization was stratified by study center and ECOG performance status (0 or 1 versus 2). The primary endpoint was the proportion of subjects with at least 1 clinically relev...

Blood Loss Management in High-Risk Patients Undergoing Total Knee Arthroplasty -A Comparison of Two Techniques

Although it is well known that patients with preoperative hemoglobin levels <13.0 g/dL are at a higher risk for requiring postoperative transfusions, the ideal blood management strategy for this group of patients remains unclear. This study compared preoperative autologous donation with preoperative administration of epoetin alfa as a method to maximize perioperative hemoglobin levels and minimize blood transfusions in these high-risk patients undergoing total knee arthroplasty (TKA). Results show that both preoperative autologous donation and epoetin alfa were successful in decreasing the need for allogeneic blood transfusions following TKA in high-risk patients. Epoetin alfa was more effective in maximizing perioperative hemoglobin levels.

HUMAN RECOMBINANT ERYTHROPOIETIN IN THE TREATMENT OF ANEMIA OF PATIENTS WITH CHRONIC RENAL FAILURE

Objective: To compare the effect of small doses of recombinant erythropoietin on anemia of patients with chronic kidney disease who need dialysis and those are not on dialysis. Design: Case-comparative study. Setting: Nephrology Department in Al-Salaam Teaching Hospital, Mosul. Methods: Eighty patients having chronic kidney disease (40 patients needed dialysis and 40 patients needed no dialysis) participated in the study. Epoetin alfa given s.c. in a dose of 4000 IU, 2 times weekly. Hemoglobin was measured before drug administration and every 2 weeks and at the end of the trial period (3 months). Result: A significant increase of hemoglobin level had been obtained after treatment with erythropoietin in both groups. Comparison between hemoglobin elevation of both groups ( 3.0 g/l for patients without dialysis and 2.9 g/l for patients with dialysis) revealed a non significant difference (P>0.5). Conclusion: the present study demonstrated that the administration of epoetin alfa, s.c. in a dose of 4000 IU twice weekly is effective in the elevation of hemoglobin levels in patients with chronic kidney disease. The effect is comparable in patients who need dialysis and in patients who need no dialysis, also the effect is similar in both sexes.

CNTO 530 functions as a potent EPO mimetic via unique sustained effects on bone marrow proerythroblast pools

AbstractAnemia as associated with numerous clinical conditions can be debilitating, but frequently can be treated via administration of epoetin-alfa, darbepoietin-alfa, or methoxy-PEG epoetin-beta. Despite the complexity of EPO-EPO receptor interactions, the development of interesting EPO mimetic peptides (EMPs) also has been possible. CNTO 530 is one such novel MIMETIBODY Fc-domain dimeric EMP fusion protein. In a mouse model, single-dose CNTO 530 (unlike epoetin-alfa or darbepoietin-alfa) bolstered red cell production for up to 1 month. In 5-fluorouracil and carboplatin-paclitaxel models, CNTO 530 also protected against anemia with unique efficiency. These actions were not fully accounted for by half-life estimates, and CNTO 530 signaling events therefore were studied. Within primary bone marrow erythroblasts, kinetics of STAT5, ERK, and AKT activation were similar for CNTO 530 and epoetin-alfa. p70S6K activation by CNTO 530, however, was selectively sustained. In vivo, CNTO 530 uniquely stimulated the enhanced formation of PODXLhighCD71high (pro)erythroblasts at frequencies multifold above epoetin-alfa or darbepoietin-alfa. CNTO 530 moreover supported the sustained expansion of a bone marrow–resident KitnegCD71highTer119neg progenitor pool. Based on these distinct erythropoietic and EPOR signaling properties, CNTO 530 holds excellent promise as a new EPO mimetic.

4: Safe and Effective Administration of Epoetin Alfa in Anemia of Sickle Cell Disease and Kidney Failure

4: Safe and Effective Administration of Epoetin Alfa in Anemia of Sickle Cell Disease and Kidney Failure

Population Pharmacokinetic Modeling of Epoetin Delta in Pediatric Patients With Chronic Kidney Disease

This analysis quantifies the population pharmacokinetics of subcutaneous and intravenous epoetin delta, an epoetin produced in a human cell line, in pediatric patients with chronic kidney disease and estimates the effects of covariate factors on epoetin delta and epoetin alfa pharmacokinetic parameters. Erythropoietin serum concentration data, taken from a phase III study conducted in 60 patients aged 1 to 17 years, were best described by a 1-compartment model with first-order absorption and elimination. The typical point estimates were clearance (0.268 L/h), central volume of distribution (1.03 L), absorption rate constant (0.0554 h(-1)), and bioavailability (0.708) for a 35-kg male < or = 10 years who was predialysis and on subcutaneous epoetin delta treatment. Erythropoietin pharmacokinetic parameters were similar in pediatric patients as compared with adults when scaled by weight. The subcutaneous administration of epoetin alfa exhibited lower systemic bioavailability than subcutaneous administration of epoetin delta.

A comparison between once-weekly and twice- or thrice-weekly subcutaneous injection of epoetin alfa: results from a randomized controlled multicentre study

In patients with chronic renal failure, the ability to reduce the administration frequency of subcutaneous (SC) erythropoietin (epoetin) could provide benefits and may improve compliance. The study investigated whether once-weekly SC epoetin alfa was equivalent to twice- or thrice-weekly SC administration in maintaining anaemia correction in haemodialysis patients. Eighty-three patients were randomly assigned to either once-weekly epoetin alfa (n = 44) or their original dose twice- or thrice-weekly regimen (control, n = 39) for 12 weeks. The haemoglobin concentration was maintained within the target range of 9.0-12.0 g/dL by adjusting the dose of epoetin alfa. All patients received intravenous iron supplementation, as required. Stable haemoglobin levels were maintained without epoetin dose increases in the majority of patients in both groups (once-weekly group, 95.0%, control group, 91.4%). The mean haemoglobin levels at randomization at weeks 4, 8 and 12 were 10.7, 11.1, 11.3 and 11.0 g/dL, respectively, in the once-weekly group, and 10.5, 11.3, 11.5 and 11.3 g/dL, respectively, in the control group. The mean weekly dose of epoetin alfa at randomization at weeks 4, 8 and 12 was 142.8, 114.5, 108.6 and 104.5 IU/kg, respectively, in the once-weekly group, and 128.4, 116.0, 101.0 and 96.1 IU/kg/week, respectively, in the control group. No statistically significant between-group differences were apparent for changes in haemoglobin levels or epoetin alfa dosages at week 12. This study demonstrates that once-weekly SC administration of epoetin alfa is as effective and safe as two or three times weekly administration in maintaining haemoglobin levels. Therefore, the once-weekly therapy using high dose of epoetin alfa is considered to be an efficient method in stable haemodialysis patients.