Epoetin Treatment Research Articles

Treating Posttransplant Anemia With Erythropoietin Improves Quality of Life but Does Not Affect Progression of Chronic Kidney Disease.

Posttransplant anemia affects 30% to 45% of kidney transplant recipients and is associated with increased morbidity. However, there is lack of evidence about safe hemoglobin levels after erythropoietin treatment. Studies are needed to better understand the potential benefits and risks, as well as to define safe target hemoglobin ranges in these patients. In this single-center exploratory, open-label randomized controlled trial, kidney trans-plant recipients with anemia 3 months posttransplant were either treated with epoetin beta to a hemoglobin target level of 11.5 to 13.5 g/dL (n = 28) or given no treatment (n = 27). Treatment effects on graft function and health quality of life were assessed. After 2 years, hemoglobin concentrations were significantly higher in the epoetin beta treatment group than in the no treatment group (12.3 ± 0.18 vs 9.99 ± 0.22 g/dL; P < .0001). Estimated glomerular filtration rate, calculated by Modified Diet in Renal Disease 7, declined by 1.7 mL/min (interquartile range, -6 to 4.24) in the epoetin treatment group and by 4.16 mL/min (interquartile range, -12.42 to 2.78) in the no treatment group (P = .32). Rate of progression, determined by estimated glomerular filtration rate slope, was not significantly different between groups (-0.09 ± 0.1 vs -0.12 ± 0.15 mL/min for treated vs not treated; P = .78). Moreover, we observed no significant differences in proteinuria and blood pressure. Treated patients had greater improvements in the vitality and mental health domains of the Medical Outcomes Short Form Health Survey quality of life scores. Treatment of anemia in kidney transplant recipients to a hemoglobin level of 11.5 to 13.5 g/dL with erythropoietin improves some quality of life scores. The treatment was safe and not associated with adverse outcomes. There were no changes in rate of decline of graft function.

Combination with intravenous iron supplementation or doubling erythropoietin dose for patients with chemotherapy-induced anaemia inadequately responsive to initial erythropoietin treatment alone: study protocol for a randomised controlled trial

IntroductionErythropoietin (EPO) is a commonly used option in the treatment of chemotherapy-induced anaemia (CIA). However, ∼30–50% of patients fail to achieve an adequate response after initial treatment. Prior studies have...

Peginesatide to Manage Anemia in Chronic Kidney Disease Patients on Peritoneal Dialysis

♦ Peginesatide is a novel, synthetic, peptide-based pegylated erythropoiesis-stimulating agent that is designed specifically to stimulate the erythropoietin receptor. The purpose of the present study was to assess, for the first time, the efficacy and safety of peginesatide in chronic kidney disease (CKD) patients receiving peritoneal dialysis (PD) and previously on epoetin treatment. ♦ In this open-label multicenter study, 59 PD patients with CKD were converted from epoetin (alfa or beta) to once-monthly peginesatide. Doses were titrated to maintain hemoglobin levels between 10 g/dL and 12 g/dL during the 25 weeks of the study. The primary endpoint was change from baseline in mean hemoglobin values during the evaluation period (weeks 20 - 25). ♦ The mean hemoglobin value during the evaluation period was 11.3 ± 1.07 g/dL, and the mean change from baseline was 0.10 ± 1.15 g/dL (95% confidence limits: -0.24, 0.44 g/dL). During the evaluation period, most patients maintained hemoglobin levels between 10 g/dL and 12 g/dL (63.0%) and within ±1.0 g/dL of baseline (60.9%). The median weekly epoetin dose at baseline was 96.0 U/kg, and the median starting peginesatide dose was 0.047 mg/kg. Forty-three patients (72.9%) completed the study. Six patients (10.2%) received red blood cell transfusions. The observed adverse event profile was consistent with underlying conditions in the PD patient population. The most common adverse event was peritonitis (20.3%), a complication commonly associated with PD. Four deaths occurred during the study (2 related to septic shock, and 1 each to myocardial ischemia and myasthenia gravis). ♦ In this study, once-monthly peginesatide maintained hemoglobin levels in PD patients after conversion from epoetin.

Efficacy and Safety of Biosimilar Epoetin Alpha in Patients with Chronic Lymphoproliferative Syndromes and Chemotherapy-Induced Anemia: An Observational, Retrospective, Monocentric Analysis

INTRODUCTION. Chemotherapy (CHT)-induced anemia is a consequence of the myelosuppressive effect of CHT, delivered for solid or hematologic malignancies, and tends to worsen over the course of repeated cycles of therapy. Erythropoietic agents have shown their efficacy in correcting CHT-induced anemia in cancer patients, in reducing the need of blood transfusion and in improving patients’ quality of life. Epoetin (EPO) biosimilars have emerged as an alternative to originator products, sharing an equivalent mechanism of action, efficacy and safety, as a result of a rigorously conducted comparability exercise.PATIENTS AND METHODS. This study was aimed at evaluating the response to EPO alpha biosimilar (Binocrit®, Sandoz, 40,000 IU/week subcutaneously) after a 4-weeks (and 8-weeks, when applicable) treatment period, as well as the rate of CHT cycles delays or interruptions due to anemia, in 49 consecutive adult patients, affected by chronic lymphoproliferative disorders, undergoing CHT, either as a first-line induction (35 patients) or second-line or salvage treatment (14 patients), and presenting with CHT-induced anemia. The median age was 69 (range 21-90) years, with 49% of the patients older than 70. Fourteen had diffuse large B-cell lymphoma, 14 an indolent non-Hodgkin’s lymphoma, 6 had chronic lymphocytic leukemia, 5 mantle cell lymphoma, 4 T-cell lymphoma, 2 hairy cell leukemia and 1 had histiocytosis. Response to EPO was defined as an increase in hemoglobin (Hb) levels after 4 (ΔHb4) and 8 weeks (ΔHb8) of treatment of at least +1 g/dL, or as the achievement of Hb > 11 g/dL independently of ΔHb, with a complete transfusion-independence. Hb stability was regarded as a ΔHb comprised between -1 and +1 g/dL. A ΔHb < -1 g/dL or an acquired transfusion dependence was judged as a lack of response. Treatment with EPO was started at the first occurrence of Hb < 10 g/dL during chemotherapy, when anemia was not due to any different concomitant cause (e.g. hemolysis, iron deficiency, malabsorption, etc). Treatment duration was established by the treating physician; however, treatment was stopped when Hb reached at least 11 g/dL, in patients whose chemotherapy programme had reached its completion and in those who became transfusion dependent.RESULTS. Mean Hb (± standard deviation) at presentation was 11.0 ± 1.6 g/dL, with 49% of patients being anemic mostly as a consequence of their disease. Nine patients had grade 2 anemia, while one presented with grade 3 anemia. Twenty-one were treated with a cyclophosphamide, doxorubicin, vincristine and prednisone (CHOP) every 21 days or with a weekly CHOP-like regimen; 10 received a fludarabine-based regimen; 6 underwent a bendamustine-based second-line treatment. The remaining 12 patients were treated with various regimens (lenalidomide, rituximab, cladribine, temsirolimus, gemcitabine). Mean Hb level at EPO treatment start was 9.3 ± 0.5 g/dL. After 4 weeks of treatment, the reached mean Hb level was 10.8 ± 1.4 g/dL for patients receiving a first-line CHT, and 11.4 ± 1.6 g/dL for those on a second or later CHT line, with a mean ΔHb4 of 1.4 ± 1.4 g/dL and 2.1 ± 1.6 g/dL for each group of patients, respectively. Sixteen patients had their Hb level measured after 8 weeks of treatment, achieving a mean Hb level of 11.0 ± 1.7 g/dL and 9.8 ± 1.4 g/dL for each treatment subgroup, with a ΔHb8 of 1.7 ± 1.6 g/dL and 0.5 ± 1.3 g/dL, respectively. Overall, 36 patients responded to the treatment, yielding to a 73.4% hematological improvement rate. Eleven patients (22.5%) showed a stable Hb level throughout their treatment course, and 2 (4.1%) were considered non-responders (figure). Among responders, 2 patients required a new biosimilar EPO alpha treatment, again with response; 2 patients showed a late recurrence of anemia, and were managed with blood transfusions. Overall, 22 patients (44.9%; 61.1% of responders) had an Hb increase of at least 2 g/dL. CHT cycles were delayed in 9 cases (18.4%) because of anemia; interruptions of the planned CHT programme occurred in 6 cases (12.2%). No adverse events were documented; in particular, no thromboembolic or pure red-cell aplasia episodes have been demonstrated.CONCLUSION. The treatment of CHT-induced anemia with biosimilar EPO alpha in patient with chronic lymphoproliferative disorders is correlated with a high rate of responses and allows a safe completion of the planned CHT programme in most of the cases, both in induction and salvage treatment settings. [Display omitted] DisclosuresBroccoli:Sandoz: Membership on an entity’s Board of Directors or advisory committees. Zinzani:Sandoz: Membership on an entity’s Board of Directors or advisory committees.

Recommended Usage of Epoetin Alpha Biosimilar Retacrit™: A Subanalysis of the Orheo Study

IntroductionChemotherapy-induced anaemia (CIA) is a frequent complication of patients (pts) with cancer, associated with fatigue and impaired quality of life, and may have serious medical consequences that can lead to discontinuation or interruption of chemotherapy (CT). Guidelines from the European Organisation for Research and Treatment of Cancer (EORTC) recommend epoetin treatment of CIA to increase haemoglobin (Hb) levels and to help to prevent red blood cell transfusions and related complications. Several epoetin alpha biosimilars are currently approved for use in the EU for the treatment of CIA. The ORHEO study (place of biOsimilaRs in the therapeutic management of anaemia secondary to chemotherapy in HaEmatology and Oncology) was a prospective, observational, non-interventional, longitudinal, national, multicentre study conducted in France that evaluated the changes in Hb level in pts with solid tumours, lymphoma or myeloma, treated with an epoetin alfa biosimilar (EAB). In this subanalysis of the ORHEO study, we compare the usage of EAB in relation to the dosage recommendations of the EORTC guidelines, with respect to efficacy and safety.MethodsPts >18 years with CIA (Hb <11 g/dL) in association with solid tumours, lymphoma or myeloma and eligible for EAB treatment were included in this study. Pts were monitored at the start of EAB therapy (D0), at 3 months (M3) and 6 months (M6). Hb response was defined as achievement of target Hb without blood transfusions in the preceding 3 weeks and during treatment or Hb ≥10 g/dL or Hb increase ≥1 g/dL since inclusion. The prescribed dosage of EAB according to body weight and the tolerability of EAB at that recommended dosage were analysed at each time point.ResultsData from 2310 pts (mean age ± standard deviation 66.5±11.8 years) from 232 centres were included in the study analysis. Overall, 79.6% of pts had solid tumours, 13.0% had lymphoma and 7.4% myeloma. Of those pts with solid tumours, 30.1% of pts had a stage III and 21.6% had a stage IV tumour. Mean baseline Hb level across all pts was 9.6 g/dL, with 35.6% of pts having moderate anaemia (Hb 8–9.5 g/dL).Almost all pts (99.9%) received the epoetin alpha biosimilar (Retacrit™, Hospira UK Ltd., median dose 30,000 IU/week). Overall, 43.8% of pts received the recommended dose of EAB (as determined by their weight) throughout the study. The proportion of pts receiving the recommended dose showed little variation between malignancies (lymphoma: 43.6%; myeloma: 40.9%; breast: 39.3%; lung: 48.3%; colorectal: 39.5%). Overall, the percentage of responders was 81.6% at M3 and 86.5% at M6. The overall mean change in Hb level was 1.5±1.6 g/dL at M3 and 1.72±1.61 g/dL at M6. Responses to treatment at M6 were similar whether or not EAB was prescribed at the recommended dose throughout the study. A similar proportion of pts receiving the recommended dose of EAB reported adverse events (AEs) at M6 compared with pts who did not receive the recommended dose (9.9 vs 9.0%). Overall, transfusion rates were 9.4% and 5.8%, while the rate of thromboembolic events was 2.4% and 1.5%, at 3 and 6 months respectively.ConclusionIn the ORHEO study, 44% of pts received the EORTC recommended dose of EAB over the 6-month course of the study. However, the response to therapy was similar regardless of dose. Furthermore, the frequency of overall AEs at M6 did not vary depending on dose.In conclusion, the EAB Retacrit™ was effective and well tolerated in the management of CIA in pts with solid tumours, lymphoma and myeloma and provides an alternative therapeutic option for the treatment of CIA. DisclosuresMichallet:MSD: Consultancy, Honoraria; Novartis: Consultancy, Honoraria; Sanofi: Consultancy, Honoraria; BMS: Consultancy, Honoraria; Astellas: Consultancy, Honoraria; Hospira: Consultancy, Honoraria. Soubeyran:Roche: Honoraria; Celgene: Honoraria; Mundipharma: Honoraria; Hospira: Honoraria. Kurtz:Hospira: Coverage of travel expenses/congress fees Other. Albrand:Hospira: Employment.

PCN197 - The German Quota System as a Model for Biosimilar Cost Savings in Epoetin Treatment

PCN197 - The German Quota System as a Model for Biosimilar Cost Savings in Epoetin Treatment

Epoetin biosimilars in the management of anemia secondary to chemotherapy in patients with solid tumors, lymphomas, and myelomas: The ORHEO study.

9564 Background: Chemotherapy may induce anemia with potentially severe consequences. The ORHEO (place of biOsimilaRs in the therapeutic management of anaemia secondary to chemotherapy in HaEmatology and Oncology) study examined the efficacy and safety of epoetin alfa biosimilars (EABs) for the treatment of chemotherapy-induced anemia (CIA) in the clinical setting. Methods: ORHEO was a multicenter, observational, prospective, post-marketing study conducted in France. Patients with CIA (Hb &lt;110g/L) &gt;18 years old, with solid tumors, lymphomas or myelomas and eligible for epoetin alfa treatment were included in the study; they received EAB as prescribed by their physician. Baseline patient characteristics and anemia-related data including baseline and target Hb level epoetin treatment, adverse events and any other concomitant treatments prescribed were recorded. The primary endpoint was the rate of responders (defined as an increase in Hb levels to 100 g/L or at least 10 g/L since inclusion visit, or reaching target Hb set at start of study, without any blood transfusions in the 3 weeks prior to measurement) at +3 months (M3). Other endpoints included rate of responders at +6 months (M6) and safety endpoints. Results: 2310 patients (51.43 % male, 48.57 % female) from 232 centers were included in this study. At baseline 79.6% had solid tumors, 13.0% lymphomas and 7.4% myelomas. Median age was 68 y (range: 18–93). Mean baseline Hb level was 96 g/L with a target Hb level of &gt;= 120 g/L for 52.7% of patients. Almost all (99.9%) received the biosimilar epoetin zeta (median dose 30,000 IU/week) with 26.6% receiving additional iron supplementation. A total of 2056 and 1664 patients had at least one Hb level value at M3 and M6 respectively. The rate of response was 81.6% and 86.5% at M3 and M6, respectively. In total, 17.0% of treated patients reported clinically relevant adverse events (all grades), the most common being infections (5.0%) and thromboembolic events (3.5%). Transfusion rates were reported as 9.4% and 5.8% at M3 and M6, respectively. No EAB-related deaths were reported. Conclusions: EAB was effective and well-tolerated in the management of CIA. Clinical trial information: NCT01626547.

Randomized Trial of Short-Course High-Dose Erythropoietin in Donation After Cardiac Death Kidney Transplant Recipients

Eryhropoiesis-stimulating agents have demonstrated tissue-protective effects in experimental models of ischemia-reperfusion injury. PROTECT was a 12-month, randomized, double-blind, placebo-controlled, single center study with high-dose recombinant human erythropoietin-β (Epoetin) in 92 donation after cardiac death (DCD) kidney transplant recipients. Patients were randomized to receive an intravenous bolus of Epoetin (3.3 × 10(4) international unit (IU); n = 45) or placebo (saline 0.9% solution; n = 47) on 3 consecutive days, starting 3-4 h before the transplantation and 24 h and 48 h after reperfusion. The immunosuppressive regimen included an anti-CD25 antibody, steroids, mycophenolate mofetil and delayed introduction of cyclosporine. Primary end point was a composite of the incidence of primary nonfunction and delayed graft function, either defined by spontaneous functional recovery or need for dialysis in the first week. Secondary objectives included duration of delayed function, renal function and proteinuria up to 1 year and thrombotic adverse events. Results showed no differences in the incidence or duration of delayed graft function and/or primary nonfunction (Epoetin 77.8 vs. placebo 78.7%, p = 1.00). Epoetin treatment significantly increased the risk of thrombotic events at 1 month and 1 year (Epoetin 24.4% vs. placebo 6.4%, p = 0.02).

Sciatic Nerve of Diabetic Rat Treated With Epoetin Delta: Effects on C-Fibers and Blood Vessels Including Pericytes

In diabetes mellitus (DM) reduced motor and sensory properties of peripheral nerves are linked with the dysfunction of neural vasculature. We investigated C-fibers and microvessels of sciatic nerve of normal, DM, and DM + epoetin delta-treated rats. C-fibers immunoreactive for calcitonin gene-related peptide (CGRP), tyrosine hydroxylase (TH), epoetin receptor (EpoR), and common beta receptor subunit of the interleukin 3 receptor (IL-3Rbeta) were present in all rats, whereas in DM and epoetin-treated rats C-fibers also showed neuronal (nNOS) and inducible (iNOS) nitric oxide synthases. The cross-sectional area of CGRP-positive C-fibers was decreased in DM, but it recovered after epoetin treatment. In all conditions, vascular endothelium showed scarce immunolabeling for endothelial nitric oxide synthase (eNOS); the profound immunoreactivity for eNOS, EpoR, and IL-3Rbeta was in pericytes. Some perivascular autonomic nerves were damaged and IL-3Rbeta positive. Findings are discussed in terms of declined sensory conduction velocity in DM, its improvement after epoetin treatment, and the possible vascular contribution to these phenomena.

Comparative efficiency and hemorheological consequences of hemotransfusion and epoetin therapy in anemic cancer patients

The aim of our study was to compare hemorheological consequences of hemotransfusion and recombinant human erythropoetin treatment in anemic cancer patients. Forty anemic patients with solid nonmyeloid malignancies were enrolled in this prospective, open-label study. Both prior to and following treatment (epoetin beta, 10,000 units subcutaneously thrice weekly, for four weeks and transfusion of 400 ml of erythrocyte mass) hemorheological measurements including blood and plasma viscosity, hematocrit (Hct), hemoglobin, red blood cell aggregation (RBCA) and deformability were completed. It was found an increase of Hb from 76.07+/-3.68 g/l to 87.86+/-4.26 g/l after the transfusion. It was accompanied by Hct rise by 25% (from 23.67+/-1.85 to 29.50+/-1.96%, p<0.05). Under these conditions the whole blood viscosity (BV) was increased by 19% (p<0.05). Plasma viscosity did not change markedly. Therefore the main cause of the whole blood viscosity rise was an increase of Hct. After erythrocyte mass transfusion there were some increases of red cell deformability and aggregation (by 7%, p>0.05). Under these conditions the Hct/BV ratio as an index of oxygen transport efficiency was changed after transfusion only slightly. While after four weeks of epoetin treatment the hematocrit/viscosity ratio was raised by 14% (p<0.05), in spite of the high blood viscosity. In addition RBCA decreased (p<0.01) and their deformability was increased by 14% (p<0.05). In vitro microrheological data permit to suggest that epoetin has a direct effect on the microrheological properties of red cells due to activation of the cellular signal transduction system including the tyrosine kinases and phosphatases. Thus, Epoetin beta administered s.c. thrice weekly, during four weeks, increased hemoglobin levels, improved hemorheological profile and especially its microrheological part as well as the blood transport capacity in anemic cancer patients who were receiving chemotherapy and its hemorheological effect was more positive than under hemotransfusion.

Effects of endurance training on extrarenal potassium regulation and exercise performance in patients on haemodialysis

Haemodialysis patients (HDP) with anaemia display impaired plasma K(+) regulation during exercise and poor exercise performance. Epoetin treatment and exercise training improve exercise performance in HDP, but whether this is associated with improved K(+) regulation is unknown. Six HDP with near-normal [Hb] were tested for aerobic power ( ) and plasma [K(+)] during incremental exercise; quadriceps muscle strength (peak torque, PT) from 0 to 360 degrees s(-1) and fatiguability (decline in strength during thirty contractions). Tests were conducted at baseline, after 6 weeks of normal activity (pre-train) and following 6 weeks cycle training (post-train). Six healthy untrained controls (CON) matched for age, sex, mass and height were tested at baseline. In HDP at baseline, and PT from 0 to 360 degrees s(-1) were respectively reduced by 37% and 27-42%, compared to CON (P < 0.05). Plasma [K(+)], the rise in [K(+)] (Delta[K(+)]) and the Delta[K(+)] relative to total work done (Delta[K(+)] work(-1) ratio) during incremental exercise were all higher in HDP at baseline compared to CON (P < 0.05). Exercise training increased time to fatigue by 12% (P < 0.05) but did not improve K(+) regulation or . An inverse correlation was found between the Delta[K(+)] work(-1) ratio and for pooled CON and HDP data. In HDP treated with epoetin, poor exercise performance was related to impaired extrarenal K(+) regulation, whilst training improved exercise performance but not K(+) regulation. Thus, although impaired extrarenal K(+) regulation may contribute to poor exercise performance in HDP, exercise performance can still improve with training despite unchanged K(+) regulation.

Sialic acid content in erythrocyte membranes of patients on chronic hemodialysis

Sialic acids (SA) located in erythrocyte membranes (EM) play an important role in the survival of circulating red blood cells. The aim of the present study was to evaluate the SA content in EM obtained from patients on chronic hemodialysis (HD) and to examine the relationships between SA and hematological parameters. Moreover, the effects of HD, treatment with human recombinant erythropoetin (epoetin), and some biochemical and hematological parameters were analyzed. The total protein (TP) and total sialic acids (TSA), together with SA bound with proteins (PBSA) and lipids (LBSA), were determined in EM of 72 HD patients and compared with the control group of healthy individuals (CG; n=25). The adequacy of HD, weekly epoetin doses, mean arterial pressure (MAP), comorbidity score, serum levels of albumin, intact parathyroid hormone (iPTH), low-density lipoprotein cholesterol (LDL-cholesterol) were estimated in patients. Compared to the CG, HD patients had higher levels of TSA (p < 0.001), PBSA (p < 0.001), LBSA (p <0.001) and decreased TP levels (p < 0.001). The TP (p < 0.045) and PBSA (p < 0.05) levels were higher in patients with diabetic nephropathy than in non-diabetic HD patients. In HD patients there were correlations between TSA, PBSA in EM and some hematologial parameters. There were no relationships between the TSA, PB content in EM and variables such as HD, epoetin treatment, MAP comorbidity score, albumin, iPTH, and LDL-cholesterol. The results of the current study demonstrated there are significantly higher levels of TSA, PBSA, LBSA and lower TP levels in EM obtained from HD patients compared to healthy subjects. Comorbidity score, epoetin and HD treatment, MAP, iPTH, albumin and LDL cholesterol had no influence on SA levels in EM of patients.

Diagnose der Rheuma-Anämie

Anaemia of chronic disease is frequently accompanied by marked disturbances in iron metabolism driven, to a large part, by liver-derived hepcidin. Typically, there is reduced iron resorption from the intestine as well as increased uptake and retention of iron within cells of the reticuloendothelial system, resulting in a diversion of iron from the circulation to storage sites with a subsequent lack of iron for red progenitor cells and iron-deficient erythropoesis. In addition, gastrointestinal blood loss may aggravate the availability of iron. By using biochemical markers and special red blood cell indices, all three compartments of iron metabolism can be readily monitored. Serum ferritin represents storage iron, whereas the transferrin saturation (TSAT) is a measure for the amount of iron bound to transferrin. Determination of red cell indices such as% hypochromic erythrocytes or reticulocyte hemoglobin (CHr) or the soluble transferrin receptor (sTfR) provides direct information on iron availability for erythropoesis. An absolute iron deficiency is characterised by a serum ferritin<30 μg/L and reduced haemoglobin levels (iron deficiency anaemia). A latent iron deficiency is characterised by reduced iron stores with still normal haemoglobin values. Patients suffering from chronic inflammation might become anaemic (Hb reduced) in the presence of adequate iron stores (ferritin normal), due to hepcidin-mediated retention of iron in the reticuloendothelial system and subsequent iron-deficient erythropoesis. Iron-restricted blood formation may also occur during epoetin treatment, when the pharmacologically stimulated erythropoesis needs more iron than transferrin (low TSAT) is able to deliver to the bone marrow. Both scenarios would ultimately lead to iron-deficient erythropoesis, which is also called functional iron deficiency. Normally it is not necessary to determine all iron parameters in each and every case. The simultaneous evaluation of storage iron (ferritin) and iron availability to the bone marrow (% hypochromic red cells, CHr or sTfR) appears to be a rational first step to characterise complex disturbancies of iron homeostasis.

Hemorheological changes in solid tumor patients after treatment with recombinant erythropoetin

The subject of this study was the effect of erythropoetin (Epoetin) treatment of anemic patients (n=30) with solid tumors on parameters of hemorheological profile. Both prior to and following Epoetin treatment (10,000 units subcutaneously thrice weekly) for four weeks hemorheological measurements included plasma and red blood cell (RBC) suspension viscosity; high and low shear whole blood viscosity; hematocrit (Hct), hemoglobin, RBC aggregation (RBCA) and deformation. It was found that the patients had reduced Hb up to 92.96+/-2.99 g/l, and the Hct - 28.2%. These parameters were significant increased after four weeks of Epoetin treatment: Hb by 28% (p<0.01) and Hct by 31% (p<0.01). In macrorheological part of the profile, both the high shear blood viscosity, and the low one were increased by 23 and 27% (p<0.05), respectively. These changes were mainly associated with the Hct rise. As for microrheological part of profile after Epoetin treatment, RBCA was decreased by 25% (p<0.05). While the red cell rigidity index (Tk) was lowered only slightly (by 8%). RBC incubation with Epoetin (10.0 I.E./ml) was accompanied by 10% decrease of Tk. It is important to note that before Epoetin treatment incubation with it led to decrease of RBCA by 30% (p<0.05), whereas after four week of the treatment period a 27% (p<0.05) rise of aggregation was found in majority of patients. Thus these results suggest that Epoetin is an effective, safe and convenient therapy for the management of anaemia in patients with cancer. And this drug has a moderate positive hemorheological effect on RBC and on the microrheological properties in particular. These data suggested that Epoetin has an effect on the membrane properties regulating RBC aggregation and deformation and affects by the signal transduction system, including Ca2+-dependant signaling pathway and tyrosine kinase and phosphotase activity change.

Ferric gluconate treatment provides cost savings in patients with high ferritin and low transferrin saturation

A subgroup of hemodialysis patients experience high serum ferritin and low tansferrin saturation for reasons not clearly understood. Here we determined the economic impact of administering sodium ferric gluconate complex to patients with serum ferritin levels higher than 500 ng/ml and a transferrin saturation less than 25% based on the Dialysis Patients Response to IV Iron with Elevated Ferritin (DRIVE) study and its extension, DRIVE II. A cost effectiveness model was developed, consistent with the DRIVE studies, using decision analysis with a 12-week time horizon. The primary effectiveness measure was the mean hemoglobin increase in the intent to treat patient groups comparing epoetin with or without sodium ferric gluconate complex. Costs were computed using projected 2007 US Medicare reimbursements for the treatments and for serious adverse events, with the effectiveness factored by the increase in hemoglobin. The net savings for sodium ferric gluconate complex plus epoetin treatment was $1390 compared to epoetin alone for each g/dl hemoglobin increase over 12 weeks of study. Sensitivity analyses were performed to test the impact of change in the variables (using medians or means and actual 2005 or projected 2007 Medicare reimbursements) and these affirmed the robustness of the model. Our study shows that treatment of patients with high ferritin and low transferrin saturation levels, as defined in DRIVE, with sodium ferric gluconate complex and epoetin resulted in significant savings compared to epoetin alone.

Association of anemia and erythropoiesis stimulating agents with inflammatory biomarkers in chronic kidney disease

Inflammatory cytokines are important predictors of cardiovascular mortality especially in patients with chronic kidney disease. Here we explored the relationship of anemia and epoetin treatment to inflammatory cytokine levels in patients with chronic kidney disease. One hundred non-dialysis patients with chronic kidney disease over 18 years of age were evenly split into anemic and non-anemic cohorts. Of the 50 anemic patients, 23 were receiving erythropoiesis stimulating agents treatments. Levels of tumor necrosis factor (TNF)-alpha were found to be significantly higher and serum albumin was significantly lower with trends towards higher interleukin (IL)-6 and IL-8 in anemic compared to non-anemic patients. Further analysis by multiple logistic regression found that anemic patients treated with erythropoiesis stimulating agents had significantly higher odds for the upper two quartiles for IL-6, IL-8 and TNF-alpha compared to non-anemic patients. Our study found that the anemia of chronic kidney disease was associated with up regulation of TNF-alpha, and possibly IL-6 and IL-8 along with increased levels of these proinflammatory cytokines in patients treated with epoetin.

The effect of epoetin dose on hematocrit

Nearly all dialysis patients receive epoetin therapy to treat anemia. Using the United States Renal Data System, we monitored the 14,001 patients aged 65 and older who started dialysis and epoetin treatment in 2003-2004. We estimated the dose-response relationship for the average epoetin dose and hematocrit during a 3-month initiation and subsequent 3-month maintenance phase using a marginal structural model to adjust for measured time-dependent confounding by indication. During the initiation phase, an S-shaped dose-response relationship for average weekly epoetin dose and hematocrit response was found. Average hematocrit levels rose as the epoetin dose was increased from 9,000 to approximately 22,500 units per week. At higher doses, the effect of increasing epoetin was minimal with average hematocrit levels plateauing at 38.5%, but this was less evident in the maintenance phase. Among patients who reached this phase, doses required to maintain the hematocrit level were lower than those required to achieve similar hematocrit levels in the initiation phase. The dose-response curve found in our study suggests that published recommendations for starting dose are appropriate, and a starting dose of 7,500-15,000 units per week can maintain the hematocrit level in the desired target range of 33-36%.

C.E.R.A. Maintains Stable Control of Hemoglobin in Patients with Chronic Kidney Disease on Dialysis when Administered Once Every Two Weeks

Background/Aims: This Phase III study examined the efficacy and safety of C.E.R.A., a continuous erythropoietin receptor activator, given once every 2 weeks (Q2W) via subcutaneous or intravenous injection using pre-filled syringes, for maintaining hemoglobin (Hb) levels in patients with chronic kidney disease (CKD) on dialysis who converted directly from epoetin therapy. Methods: Patients (n = 336) were randomized 1:1 to continue epoetin at their current dose, route and administration interval (once to three times weekly (QW–TIW)), or receive C.E.R.A. Q2W by the same route as previous epoetin treatment for 36 weeks. Dosage was adjusted to maintain patients’ Hb within ±1.0 g/dl of baseline value and within 10.0–13.5 g/dl. Primary endpoint was mean change in Hb between baseline and the evaluation period (weeks 29–36). Results: Mean change in Hb for C.E.R.A. and epoetin was 0.088 and –0.030 g/dl, respectively (endpoint Hb 11.93 and 11.86 g/dl, respectively). Analysis showed that C.E.R.A. was as effective as epoetin in maintaining Hb (p < 0.0001), and was well tolerated. The administration route had no impact on primary endpoint. Conclusion: Q2W C.E.R.A. administered using pre-filled syringes effectively maintains stable control of Hb in patients on dialysis who convert directly from epoetin QW–TIW.

Intravenous methoxy polyethylene glycol-epoetin beta for haemoglobin control in patients with chronic kidney disease who are on dialysis: a randomised non-inferiority trial (MAXIMA)

Conventional treatment with epoetin to manage anaemia in chronic kidney disease needs frequent administrations, changes of dose, and close monitoring of haemoglobin concentrations. We aimed to compare the effectiveness of methoxy polyethylene glycol-epoetin beta, given intravenously at 2-week or 4-week intervals, with epoetin treatment one to three times per week for haemoglobin control in haemodialysis patients. We screened 1115 adult patients from 96 centres who had stable chronic renal anaemia and were on dialysis treatment and intravenous maintenance epoetin. We did an open-label, parallel-group, non-inferiority trial to compare two dosing intervals of methoxy polyethylene glycol-epoetin beta with standard epoetin treatment. We established baseline haemoglobin concentration and eligibility over a 4-week run-in period. 223 patients were randomly assigned to receive methoxy polyethylene glycol-epoetin beta every 2 weeks, and 224 to receive it every 4 weeks. The initial dose was based on the average epoetin dose given during the week before the switch. The primary endpoint was change in haemoglobin concentration between baseline and the assessment period. We analysed patients both by intention to treat and per protocol. This study is registered with ClinicalTrials.gov, number NCT00077610. We excluded 133 of the 673 randomised patients from the per-protocol analysis because they had inadequate iron status or fewer than five haemoglobin measurements during the assessment period or needed red blood cell transfusions. The mean change from baseline haemoglobin for patients who had switched to intravenous methoxy polyethylene glycol-epoetin beta every 2 weeks (-0.71 g/L, 95% CI -2.20 to 0.77) or every 4 weeks (-0.25 g/L, -1.79 to 1.29) was non-inferior to the mean change for patients who continued treatment with epoetin (-0.75 g/L, -2.26 to 0.75) (p<0.0001 for both comparisons). Of the 666 patients who received at least one dose of study drug, the incidence of adverse events or serious adverse events did not differ between groups (p=0.30 and p=0.40, respectively). This long-acting erythropoiesis-stimulating agent is as safe as conventional epoetin treatment, and can maintain anaemia management in haemodialysis patients when given intravenously at 4-week dosing intervals.

Epoetin treatment in haematologic malignancy: How to improve response?

Epoetin treatment in haematologic malignancy: How to improve response?