Epoetin Alfa Treatment Research Articles

Evaluation of serum ferritin level and hepatitis b and hepatitis c viral infection in chronic hemodialysis patients.

The most popular treatment for end-stage renal illness is hemodialysis (HD). The study aimed to assess serum ferritin levels and their connection to Epoetin alfa resistance, along with exploring the link between hepatitis C virus, iron overload, and the prevalence of hepatitis C and B infections in chronic HD patients. This was a descriptive-analytical study conducted on 50 Patients with chronic kidney disease (CKD) who were on regular HD in the dialysis unit of Ibin Sina Teaching Hospital in Mosul City, Iraq. Out of 50 patients, 26 (52%) tested positive for Hepatitis C Virus (HCV) Antibody, 10 (20%) for Hepatitis B surface Antigen (HBsAg), and 14 (28%) tested negative for both. Higher serum iron and ferritin levels were found in HCV antibody-positive patients (p < 0.05). Despite Epoetin alfa treatment, patients with elevated ferritin levels exhibited lower Hemoglobin (HB) and Packed Cell Volume (p < 0.05). Non-diabetics exhibited significantly higher serum ferritin, Hemoglobin, Blood urea, and serum creatinine than diabetics (p < 0.05). A noteworthy association was seen between the quantity of blood transfusions and elevated levels of serum ferritin and total serum iron (p < 0.05). Most HD patients were anemic, with Hepatitis B and C prevalent. The main CKD causes were diabetes and hypertension. HCV-positive patients often showed mild to moderate iron overload, and high serum ferritin was linked to poor Epoetin alfa response. Dialysis can elevate blood urea, ferritin, and creatinine, worsening anemia. High ferritin levels may hinder response to Epoetin alfa and iron replacement. Excessive blood transfusions can lead to iron overload and inhibit erythropoiesis. Maintaining HB at 110-120 g/l improves quality of life and reduces anemia-related risks.

Combined Treatment with Lenalidomide and Epoetin Alfa Leads to Durable Responses in Patients with Epo-Refractory, Lower Risk Non-Deletion 5q [Del(5q)] MDS: Final Results of the E2905 Intergroup Phase III Study - an ECOG-ACRIN Cancer Research Group Study, Grant CA180820, and the National Cancer Institute of the National Institutes of Health

Combined Treatment with Lenalidomide and Epoetin Alfa Leads to Durable Responses in Patients with Epo-Refractory, Lower Risk Non-Deletion 5q [Del(5q)] MDS: Final Results of the E2905 Intergroup Phase III Study - an ECOG-ACRIN Cancer Research Group Study, Grant CA180820, and the National Cancer Institute of the National Institutes of Health

Prolonged response to recombinant human erythropoietin treatment in patients with myelodysplastic syndrome at a single referral centre in Brazil

OBJECTIVES:To evaluate the effects of epoetin (EPO) alfa treatment on overall survival, event-free survival and response duration in patients with myelodysplastic syndrome (MDS) who were treated at a haematological referral centre in northeastern Brazil.METHODS:This was a retrospective cohort study of 36 patients diagnosed with MDS and treated with EPO alfa at 30,000 to 60,000 IU per week. Clinical data were collected from medical records. The events assessed were non-response to treatment and progression to acute myeloid leukaemia (AML). Statistical analyses were performed using GraphPad Prism 7 and SPSS 24 software.RESULTS:The overall survival of patients who received EPO alfa treatment was 51.64%, with a median of 65 months of treatment, and the overall survival of this group was 100% during the first 24 months. We detected a 43.5-month median event-free survival, with a response rate of 80.5%. We observed responses from 25 to 175 months. Patients with transfusion dependence and those with a high-risk stratification, as determined by the International Prognostic Scoring System (IPSS), the Revised International Prognostic Scoring System (IPSS-R), the WHO classification-based Prognostic Scoring System (WPSS) and the WHO 2016, had a lower event-free survival than other patients.CONCLUSIONS:Despite the wide use of EPO alfa in the treatment of anaemia in patients with MDS, the median response duration is approximately only 24 months. Our data provide encouraging results concerning the benefits of using EPO alfa for the improvement of the quality of life, as patients treated with EPO showed higher overall survival, event-free survival rates and longer response durations than have been previously described in the literature.

Early High-Dose Erythropoietin Therapy After Out-of-Hospital Cardiac Arrest: A Multicenter, Randomized Controlled Trial

BackgroundPreliminary data suggested a clinical benefit in treating out-of-hospital cardiac arrest (OHCA) patients with a high dose of erythropoietin (Epo) analogs. ObjectivesThe authors aimed to evaluate the efficacy of epoetin alfa treatment on the outcome of OHCA patients in a phase 3 trial. MethodsThe authors performed a multicenter, single-blind, randomized controlled trial. Patients still comatose after a witnessed OHCA of presumed cardiac origin were eligible. In the intervention group, patients received 5 intravenous injections spaced 12 h apart during the first 48 h (40,000 units each, resulting in a maximal dose of 200,000 total units), started as soon as possible after resuscitation. In the control group, patients received standard care without Epo. The main endpoint was the proportion of patients in each group reaching level 1 on the Cerebral Performance Category (CPC) scale (survival with no or minor neurological sequelae) at day 60. Secondary endpoints included all-cause mortality rate, distribution of patients in CPC levels at different time points, and side effects. ResultsIn total, 476 patients were included in the primary analysis. Baseline characteristics were similar in the 2 groups. At day 60, 32.4% of patients (76 of 234) in the intervention group reached a CPC 1 level, as compared with 32.1% of patients (78 of 242) in the control group (odds ratio: 1.01; 95% confidence interval: 0.68 to 1.48). The mortality rate and proportion of patients in each CPC level did not differ at any time points. Serious adverse events were more frequent in Epo-treated patients as compared with controls (22.6% vs. 14.9%; p = 0.03), particularly thrombotic complications (12.4% vs. 5.8%; p = 0.01). ConclusionsIn patients resuscitated from an OHCA of presumed cardiac cause, early administration of erythropoietin plus standard therapy did not confer a benefit, and was associated with a higher complication rate. (High Dose of Erythropoietin Analogue After Cardiac Arrest [Epo-ACR-02]; NCT00999583)

Clinical benefits and risks associated with darbepoetin alfa and epoetin alfa treatment in patients with lung cancer and chemotherapy-induced anemia.

e21635Background: Chemotherapy-induced anemia (CIA) is a frequent complication in lung cancer (LC). One option for the management of this anemia is the administration of recombinant human erythropo...

Treatment of Chemotherapy-Induced Anemia Using Epoetin Alfa Biosimilar for Patients with Lymphoma and Myeloma: The Synergy Study

Background Recommendations on erythropoiesis-stimulating agents for the management of chemotherapy-induced anemia (CIA) are well established (Schrijvers D et al. Ann Oncol 2010;21[suppl 5]:v244-7). Iron supplementation can further improve treatment response of CIA, particularly in the case of iron deficiency (Pedrazzoli P et al. J Clin Oncol 2008;26:1619-25; Auerbach M et al. J Clin Oncol 2004;22:1301-7), but is under-used. Objective To evaluate the effect of epoetin alfa biosimilar, with or without iron, on CIA in current oncology and hematology practice. Methods SYNERGY was an observational, longitudinal, prospective, multicenter study conducted in France, from a representative, random sample of oncologists and hematologists. Patients of these clinicians were aged ≥18 years with solid tumors, lymphoma and/or myeloma and CIA, eligible for treatment with epoetin alfa biosimilar and followed for 12-16 weeks. A subanalysis of patients with lymphoma or multiple myeloma is presented here. Results Overall, 2167 patients were enrolled by 195 French oncologists and hematologists during June 2012-December 2014. Of these patients, 12.7% (n=264) had lymphoma and 6.6% (n=136) had multiple myeloma and were included in the analysis population, where the disease categories were non-exclusive; 84.5% (n=223) of patients with lymphoma were diagnosed with non-Hodgkin's lymphoma. Half of the patients with lymphoma and multiple myeloma were male. The majority of patients were ≥70 years old (60.6% of patients with lymphoma and 69.1% with multiple myeloma) and had a performance status of 0 or 1 (72.9% [n=180] of patients with lymphoma and 71.8% [n=94] with multiple myeloma). Baseline mean ± standard deviation (SD) hemoglobin (Hb) levels of patients with lymphoma and multiple myeloma were 9.5±0.8 g/dL and 9.5±0.9 g/dL; 40.2% (n=106) and 39.0% (n=53) of these patients had moderate anemia (Hb 8.0-9.5 g/dL), while 2.3% (n=6) and 4.4% (n=6) had severe or very severe anemia (Hb ≤8.0 g/dL), respectively. Iron status assessment was available for 60.2% (n=159) of patients with lymphoma and for 59.6% (n=81) with multiple myeloma. Concomitant iron supplementation was not prescribed with epoetin alfa biosimilar for the majority of patients. A total of 11.4% (n=30) of patients with lymphoma and 6.6% (n=9) of patients with multiple myeloma received iron, of whom 63.3% (n=19) and 77.8% (n=7) were prescribed oral iron formulations, respectively. Patients who reached their target Hb level (increase of ≥1 g/dL since enrollment or an increase of ≥2 g/dL, with no transfusions in the three previous weeks) was 79.1% (n=201) of patients with lymphoma and 84.6% (n=104) of patients with multiple myeloma, higher than the overall analyzed population (74.2%, n=1390). The response rate to epoetin alfa biosimilar (epoetin alfa biosimilar discontinued as Hb &gt; target level, with no transfusions in the three previous weeks) was lower in patients with lymphoma given iron supplementation versus those not given iron; 66.7% (n=20) of the iron supplementation group were responders, compared with 75.4% (n=169) of patients without iron. Response to epoetin alfa biosimilar was similar in patients with multiple myeloma regardless of the iron supplementation status (85.7% [n=6] of patients with iron supplementation and 81.0% [n=94] of patients without). The response to epoetin alfa biosimilar translated into an improvement in patient perception of fatigue (66.7% [n=20] of patients with iron supplementation and 72.5% [n=161] of patients without who had lymphoma; 71.4% [n=5] of patients with iron supplementation and 81.3% [n=91] of patients without who had multiple myeloma). Conclusions These results indicate that epoetin alfa biosimilar was effective in treating patients with CIA and lymphoma/myeloma in France and agrees with previous studies (Michallet M et al. BMC Cancer 2014;14:503). Iron supplementation did not appear to increase the response to epoetin alfa treatment in this population; however, confirmatory studies in larger patient cohorts are required. Disclosures Scotté: Hospira SAS: Research Funding. Laribi:Hospira SAS: Research Funding. Gisselbrecht:Hospira SAS: Research Funding; Roche: Consultancy, Research Funding; Baxter: Research Funding; Chugai Pharmaceutical: Research Funding; Bertram Glass: Research Funding. Spaeth:Hospira SAS: Research Funding. Kasdaghli:Hospira: Employment. Albrand:Hospira: Employment. Leutenegger:GECEM: Employment; Hospira SAS: Research Funding. Ray-Coquard:Hospira SAS: Research Funding; Amgen: Consultancy, Other: Paid instructor; PharmaMar: Consultancy, Other: Paid instructor; Roche: Consultancy, Other: Paid instructor.

INFLUENCE OF EPOETIN ALFA ON LEVEL OF PROINFLAMMATORYAND ANTIINFLAMMATORY CYTOKINE OF PATIENTS IN MAINTENCE HEMODIALYSIS

Summary. The aim of the present research was to study the influence of еpoetin alfa to the level of pro- and anti-inflammatory cytokines in patients with anemia treated by hemodialysis (HD).&#x0D; Materials and methods: We examined 73patients with anemia treated by hemodialysis (mean age 45,85 ±1,21 years). Patients were divided into 2groups: I group - comparison (n = 32), II group - treatment by epoetin alfa (n = 41). The levels of hemoglobin, C-reactiveprotein, ferritin, albumin, pro-and anti-inflammatory cytokines were determined before and after treatment in patients of both groups. The duration of treatment was 5 months.&#x0D; Results: Epoetin alfa increases Hb levels in patients treated by HD. After epoetin alfa applying reduction of proinflammatory cytokines ( TNF -a, IL -ip, IL -17, IL -18) and increased levels of IL -10 were observed.&#x0D; Conclusions: The clinical efficacy of the epoetin alfa treatment at the moment of completion of treatment was 75.6% (level of Hb &gt; 110 g/L ). Epoetin alfa, improving the level of Hb, reduces the activity of chronic inflammation.

CP-096 Biosimilar epoetin zeta in the treatment of chemotherapy-induced anaemia

BackgroundBiosimilars are used at the same dose as the reference product to treat the same disease and may offer cost savings in clinical practice. Epoetin zeta is an epoetin biosimilar...

Adding Epoetin Alfa to Intense Dose-Dense Adjuvant Chemotherapy for Breast Cancer: Randomized Clinical Trial

BackgroundThe AGO-ETC trial compared 5-year relapse-free survival of intense dose-dense (IDD) sequential chemotherapy with epirubicin (E), paclitaxel (T), and cyclophosphamide (C) (IDD-ETC) every 2 weeks vs conventional scheduled epirubicin/cyclophosphamide followed by paclitaxel (EC→T) (every 3 weeks) as adjuvant treatment in high-risk breast cancer patients. The objective of this study was to evaluate the safety and efficacy of epoetin alfa in a second randomization of the intense dose-dense arm.MethodsOne thousand two hundred eighty-four patients were enrolled; 658 patients were randomly assigned to the IDD-ETC treatment group. Within the IDD-ETC group, 324 patients were further randomly assigned to the epoetin alfa group, and 319 were randomly assigned to the non–erythropoiesis-stimulating agent (ESA) control group. Primary efficacy endpoints included change in hemoglobin level from baseline to Cycle 9 and the percentage of subjects requiring red blood cell transfusion. Relapse-free survival, overall survival, and intramammary relapse were secondary endpoints estimated with Kaplan-Meier and Cox regression methods. Except for the primary hypothesis, all statistical tests were two-sided.ResultsEpoetin alfa avoided the decrease in hemoglobin level (no decrease in the epoetin alfa group vs –2.20g/dL change for the control group; P < .001) and statistically significantly reduced the percentage of subjects requiring red blood cell transfusion (12.8% vs 28.1%; P < .0001). The incidence of thrombotic events was 7% in the epoetin alfa arm vs 3% in the control arm. After a median follow-up of 62 months, epoetin alfa treatment did not affect overall survival, relapse-free survival, or intramammary relapse.ConclusionsEpoetin alfa resulted in improved hemoglobin levels and decreased transfusions without an impact on relapse-free or overall survival. However, epoetin alfa had an adverse effect, resulting in increased thrombosis.

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.

Propensity score matched assessment of treatment patterns and cost of erythropoiesis stimulating agent treatment in patients with cancer receiving myelosuppressive chemotherapy

To examine epoetin alfa (EPO) and darbepoetin alfa (DARB) treatment patterns and erythropoiesis stimulating agent (ESA) costs in patients with cancer receiving chemotherapy (CRC), and to compare the results observed in the pre-matched total study population (TSP) with a propensity score matched population (PSMP). A medical claims analysis was conducted from 1 January 2004 through 31 July 2009 using the HealthCore Integrated Research Database. Patients were at least 18 years old, newly initiated on EPO or DARB, received ≥ 2 ESA doses, and had ≥ 1 claim for cancer and chemotherapy proximate to ESA treatment. Patients were matched using propensity scores. January 2010 Wholesale Acquisition Cost was used to calculate drug cost. Mean cumulative ESA dose and drug costs were evaluated in the TSP and PSMP. 4921 EPO and 9173 DARB patients with CRC were identified. In the TSP, mean cumulative ESA doses were EPO: 398,770 units and DARB: 1508 mcg, with similar treatment durations for each. Mean cumulative drug costs were EPO: $6041 and DARB: $7861 (30% higher for DARB). The cumulative dose ratio (EPO units: DARB mcg) was 264:1. The PSMP analysis identified 4831 ESA treated CRC patients in each group. Mean drug costs were EPO: $6055 and DARB: $7863 (30% higher for DARB). The observed dose ratio (EPO units: DARB mcg) was 265:1. In both analyses, the costs of DARB were higher, even after accounting for baseline differences in the PSMP. Similar trends in dose ratios were also observed in both groups.

Dutch observational study on anemia management with epoetin alfa.

e19525 Background: The medical practice with epoetin alfa (Eprex) treatment (ET) for chemotherapy-induced anaemia (CIA) in the Netherlands was evaluated with regards to safety and efficacy in this observational study enrolling 1927 patients (pts) from 2005 to 2009. Methods: Eligible pts were ≥18 years and diagnosed with a solid tumour, multiple myeloma or (non-)Hodgkin’s disease for which chemotherapy (CT) was initiated. Data on haemoglobin level (Hb), blood transfusions (BT), CT, ET, iron supplementation and treatment-emergent adverse events (TEAE) were collected. Hb response to ET, not influenced by a transfusion within 28 days prior to reaching response, was defined in the protocol as ≥1 g/dl Hb rise within first 4 weeks ET or ≥2 g/dl Hb-rise from baseline or Hb within range 11–13 g/dl after 4 weeks of ET until end of study. Results: Average age was 63.2 years, 46.9% were male. Median mode dose was 40.000 IU/week. Most pts had lung (48.9%), breast (13.0%) or gastro-intestinal (9.9%) tumours. Majority of pts had metastatic disease (61.2%) and received platinum-containing CT (66.6%). ET generally started during the first 3 cycles of CT (79.1%). During CT, iron supplementation occurred in 23.8% of pts (mostly oral iron). Median ET duration was 10 weeks (95% CI: 11.38-12.09 weeks). ET response was reached in 61.9% of pts. ET started at an Hb of 10.52±1.11 g/dl (n=1182) and resulted in a transfusion-independent Hb-rise of 0.48±1.72 g/dl after 4 weeks (28–35 days) (n=891, p<0.0001) and 1.31±2.05 g/dl after 8 weeks (56–63 days) (n=623, p<0.0001). In 18.8% of pts, a BT was given beyond the first 4 weeks of ET. TEAEs were reported in 77.2% of patients; 1.5% of events were related to ET upon investigator assessment. Thrombovascular TEAE’s (TVE) occurred in 152 pts (7.9%); 35 events were assed as having a causal relation to ET. During study 207 pts died, the majority (n=143) due to disease progression. Six pts died due to a TVE: cerebrovascular accident (3), myocardial infarction (1) and pulmonary embolism (2); none assessed to be related to ET. Conclusions: Results of this Dutch study show that ET generally started according to published guidelines for the treatment of CIA. ET significantly increased Hb in pts with CIA and TEAEs seem in line with current label for epoetin alfa.

Propensity score matched evaluation of epoetin alfa and darbepoetin alfa utilization in patients with cancer receiving chemotherapy.

e16518 Background: To examine epoetin alfa (EPO) and darbepoetin alfa (DARB) treatment patterns and erythropoiesis stimulating agent (ESA) costs in patients with cancer receiving chemotherapy (CRC). Additionally, we compared the results observed in the total study population (TSP) with a propensity score matched population (PSMP) to account for potential baseline difference that may affect ESA utilization. Methods: A medical claims analysis was conducted from 1/1/2004-7/31/2009 using the HealthCore Integrated Research Database. Patients were age ≥18 years, newly initiated on EPO or DARB, received ≥2 ESA doses, and had ≥1 claim for cancer and chemotherapy proximate to ESA treatment. Patients with myeloid leukemia, chronic kidney disease, receiving dialysis, or treated with both agents were excluded. Propensity score matching was used to identify similar populations in the EPO and DARB groups. January 2010 wholesale acquisition cost was used to calculate drug cost. Mean cumulative ESA dose and drug costs we...

A secondary analysis of the CHOIR trial shows that comorbid conditions differentially affect outcomes during anemia treatment

The CHOIR trial in anemic patients with chronic kidney disease compared epoetin-alfa treatment with low (11.3 g/l) and high (13.5 g/l) hemoglobin targets on the composite end point of death, hospitalization for heart failure, stroke, and myocardial infarction. However, other anemia management trials in patients with chronic kidney disease found there was increased risk when hemoglobin is targeted above 13 g/dl. In this secondary analysis of the CHOIR trial, we compared outcomes among the subgroups of patients with diabetes and heart failure to describe the comparative relationship of treatment to these two different hemoglobin goals. By Cox regression analysis, there was no increased risk associated with the higher hemoglobin target among patients with heart failure. In patients without heart failure, however, the hazard ratio (1.86) associated with the higher target was significant. Comparing survival curves in an unadjusted model, patients with diabetes did not have a greater hazard associated with the higher target. Subjects without diabetes had a significantly greater hazard in the high as compared to the low target, but the interaction between diabetes and the target was not significant. We suggest that the increased risks associated with higher hemoglobin targets are not clinically apparent among subgroups with greater mortality risk. These differential outcomes underscore the need for dedicated trials in these subpopulations.

The Importance of Clinical Variables in Comparative Analyses Using Propensity-Score Matching

The erythropoiesis-stimulating agents (ESAs) epoetin alfa (EA) and darbepoetin alfa (DA) have comparable efficacy in treating chemotherapy-induced anaemia (CIA). Therapy choice depends on many factors, including cost. Previous estimates of ESA cost differences have been derived from claims data. These data lack clinical variables, such as baseline haemoglobin (Hb) level, which are likely to influence choice of ESA, dosing and costs. We estimated cost differences between DA and EA in patients with cancer receiving chemotherapy, using a propensity-score matched analysis of baseline patient characteristics with and without Hb values to assess the effect of this clinical variable on ESA cost estimates. Data were extracted from electronic medical records in two US databases between January 2004 and December 2006. The study sample included 6743 patients receiving chemotherapy, with one or more visits during the study period, who received an ESA during a chemotherapy episode. Episodes of chemotherapy care were constructed using a 90-day gap in administration to identify the start and end. Patients receiving both DA and EA during their initial chemotherapy episode or with missing data were excluded, representing 42% of patients with CIA receiving an ESA. Drug costs were calculated from the cumulative dose multiplied by 106% of the average sales price (ASP) for DA or EA. Two propensity-score matches were conducted: first using variables available in administrative billing claims systems, then adding the baseline Hb test result. Regression-adjusted cost differences were estimated with and without baseline Hb, using generalized linear models. Using baseline Hb levels resulted in a better match of the baseline characteristics for the EA and DA treatment groups than the original sample or the matched sample without Hb variables. Mean ESA costs (year 2007 values) for the original sample were $US4171 for EA and $US3811 for DA (mean difference $US360; p < 0.001, standard error [SE] $US99). With propensity-score matching without Hb variables, mean estimated costs were $US3836 for EA and $US3599 for DA (mean difference $US237; p = 0.053, SE $US123). With propensity-score match including Hb variables, mean costs were $US3965 for EA and $US3536 for DA (mean difference $US429; p = 0.001, SE $US125). Cost differences in sensitivity analyses ranged between $US102 (p = 0.201) and $US261 (p = 0.003). Addition of baseline Hb level as a variable in propensity score and ESA cost models affects ESA treatment cost estimates in patients with cancer receiving chemotherapy. Cost comparisons based on observational data should use analytical methods that account for differences in clinical variables between treatment groups.

Early hemoglobin decline and survival prognosis in epoetin alfa studies

9625 Background: When cancer patients (pts) with chemotherapy-induced anemia (CIA) respond to erythropoietic-stimulating agents (ESA), hemoglobin (Hb) typically increases within 4–8 weeks. This exploratory analysis examined whether mortality differs depending on Hb response after 4 or 8 weeks of epoetin alfa (EPO) treatment or depending on transfusion. Methods: Pt-level data were analyzed from 31 randomized studies (7,215 pts) of epoetin alfa vs non-EPO (15 studies) or placebo (16 studies) in pts with CIA. A landmark analysis was used; Hb change was set at a specific time (4 and 8 weeks) and subsequent survival was examined separately for EPO and placebo. Pts were categorized as “Hb increased” (&gt;0.5 g/dL), “Hb decreased” (&gt;0.5 g/dL), or “Hb stable” (within ±0.5 g/dL) compared to baseline. Hb stable was compared to other Hb change categories with Cox proportional hazards models, stratified by study and adjusted for potential confounders. Results: The hazard ratio (HR) for Hb decreased versus Hb stable at 4 weeks was 1.44 for EPO (95% CI: 1.04, 1.99), indicating worse survival for pts with a decline in Hb. This association was weaker for placebo (HR: 1.12; 95% CI: 0.74, 1.67). Increased risk with declining Hb in EPO-treated pts was most pronounced in studies that maintained Hb ≥12 g/dL or treated pts for &gt;12–16 weeks (1,876 pts). Patterns were similar using the 8-week landmark. In both EPO-treated and placebo pts, transfusion increased the rate of on-study death ∼3.5 fold (treating transfusion as a time-dependent variable). Conclusions: These exploratory findings suggest that both decreased Hb after 4 or 8 weeks of EPO treatment and transfusion are associated with increased risk of death. In spite of adjustment for other prognostic factors, it is likely that this association reflects poorer underlying prognosis of pts whose Hb fails to respond. ESAs should be discontinued in the absence of a Hb response. [Table: see text]

Drug utilisation and cost considerations of erythropoiesis stimulating agents in oncology patients receiving chemotherapy: observations from a large managed-care database

Objective. Erythropoiesis stimulating agent (ESA) resource utilisation in cancer chemotherapy patients is of importance to managed-care organisations. To understand current real-world utilisation of ESAs, this study examined epoetin alfa (EPO) and darbepoetin alfa (DARB) treatment patterns (dosing and treatment duration), dose ratio and ESA treatment costs.Methods. An analysis of medical claims data from January 2006 through to January 2008 was conducted using the PharMetrics Patient-Centric database of over 85 health plans. Patients included in the study were ≥18 years of age, had at least one cancer claim within 90 days prior to ESA treatment initiation, were newly initiated on EPO or DARB, received at least two doses, and were treated with concomitant chemotherapy (at least one chemotherapy claim during ESA treatment). Mean cumulative ESA dose was used to calculate drug cost (based on April 2008 wholesale acquisition cost) and dose ratio (units EPO : μg DARB).Results. A total of 4,111 EPO patients and 6,817 DARB patients met inclusion criteria and formed the study population. EPO-treated patients were slightly older (mean age: EPO 63.6, DARB 61.8, p<0.0001) with a greater proportion of women in the DARB-treated group (EPO 60.9%, DARB 64.1%, p=0.0007). The mean treatment duration was slightly longer in the EPO group (EPO 58.4 days, DARB 55.4 days, p=0.0019). The mean cumulative ESA dose administered was EPO 329,129 units and DARB 1,289 μg, resulting in a dose ratio of 255:1 (units EPO:μg DARB). Mean drug cost per treatment episode was significantly lower in the EPO group by $1,768 (EPO $4,321, DARB $6,089, p<0.0001). After controlling for covariates, the incremental cost associated with DARB treatment remained stable and statistically significant (adjusted cost difference: $1,806 per treatment episode higher for DARB patients than EPO, p<0.0001).Conclusions. This study of 10,928 oncology patients receiving chemotherapy reported a dose ratio of 255:1 (units EPO:μg DARB) with 29% lower treatment cost in the EPO group. These findings are similar to those previously reported from published clinical trials and real-world utilisation studies.

Relationship Between Epoetin Alfa (EPO) Treatment and Serum Hepcidin Levels in Anemic Patients with Rheumatoid Arthritis (RA)

Introduction: Some patients treated with EPO and oral iron supplementation respond poorly to EPO, possibly due to inflammation-induced iron sequestration. In response to inflammation, hepcidin, a hormone secreted by the liver, binds to and downregulates ferroportin, the principal cellular iron exporter. In turn, ferroportin downregulation leads to sequestration of iron in absorption sites within duodenal enterocytes, hepatocytes, and in macrophages that break down senescent red blood cells and normally recycle iron back into circulation. This sequestration results in reduced amounts of plasma iron that is bio-available for erythropoiesis. Patients with rheumatoid arthritis (RA), malignancies, or infections frequently manifest inflammatory-associated anemia and elevated hepcidin levels.Objective: To assess the impact of EPO treatment on hepcidin levels in patients with RA.Methods: Serum hepcidin levels and iron status were analyzed from a randomized, double-blind, placebo-controlled, investigational study of 29 patients with RA treated with either EPO or Placebo for 20 weeks. Serum hepcidin levels were measured at baseline and at the end of study. Serum transferrin saturation, serum ferritin, serum transferrin receptor (sTfr) levels and hemoglobin (Hb) concentrations were also measured. Patients with baseline Hb ≤11 g/dL were treated with EPO starting doses of 20,000 U subcutaneously (SQ) once weekly (QW) that could be titrated up to 40,000 U SQ QW. Oral iron was administered to keep the sTfr index <1.5. Iron restriction adequate to hinder erythropoiesis was defined by a transferrin saturation of <16%. Serum hepcidin levels of ≥300 ng/mL were considered elevated. Hematologic response to EPO was defined by achieving a Hb of ≥12 g/dL or a ≥2 g/dL increase in Hb from baseline to the end of study.Results: Iron restriction was noted in 5/15 (33%) EPO-treated patients and in 2/14 (14%) receiving Placebo. Hepcidin levels were elevated in 10/15 (67%) EPO-treated patients and in 5/13 (38%) receiving Placebo. There was a strong correlation between baseline serum hepcidin and serum ferritin levels (R= 0.5598 P=0.0019), but not serum transferrin saturation. Eleven of 15 (73%) EPO-treated patients had a Hb response compared to one of 14 (7%) receiving Placebo. Mean hepcidin levels decreased significantly from baseline in the EPO-treated patients (−155.6±186.6 EPO, 90.28±83.1 Placebo, P<0.01). As shown in the diagrams below, serum hepcidin levels appeared to decrease in EPO-treated patients, but not in those receiving Placebo, while Hb levels increased in EPO-treated patients but not in the patients receiving Placebo.Conclusion: EPO treatment may effectively elicit Hb response in patients with RA and may be associated with suppression of inflammation-induced serum hepcidin levels. Further study is warranted in conditions associated with inflammation, such as cancer and chronic renal failure, in which EPO is used to treat anemia. [Display omitted] [Display omitted]

The Importance of Clinical Variables for Propensity Score Matching When Comparing Costs: The Case of ESA Treatments for Chemotherapy Induced Anemia

Background: The erythropoiesis-stimulating agents (ESAs) epoetin alfa (EA) and darbepoetin alfa (DA) are treatments for chemotherapy-induced anemia. Therapy choice depends on many factors, including cost. Previous analyses have demonstrated differences in the characteristics of patients receiving EA vs. DA. We estimated cost differences between DA and EA in patients with cancer receiving chemotherapy using a propensity score matched analysis of baseline patient characteristics with and without hemoglobin (Hb) values.Methods: Data were extracted from electronic medical records in two US databases between January 2004 and December 2006. The study sample included 6743 patients receiving chemotherapy, with ≥ 1 visit during the study period, who received an ESA during a chemotherapy episode. Episodes of chemotherapy care were constructed using a 90 day gap in administration to identify the start and end. Patients receiving both, or neither, DA and EA during their initial chemotherapy episode, or with missing descriptive data were excluded. Drug costs were calculated from cumulative dose multiplied by 106% of the average sales price (ASP) for DA or EA. Two propensity score matches were conducted: first using variables available in administrative billing claims systems, then adding the baseline Hb test result. Regression-adjusted cost differences were estimated with and without baseline Hb, using generalized linear models.Results: Using baseline Hb as a variable resulted in a better match of the baseline characteristics for the EA and DA treatment groups compared to the original sample or the matched sample without baseline Hb. Mean ESA costs for the original sample were $4171 for EA and $3811 for DA (mean difference: $360; P <0.001, SE $99). With propensity score matching without baseline Hb, mean estimated costs were $3836 for EA and $3599 for DA (mean difference: $237; P = 0.053, SE $123). With propensity score match including baseline Hb, mean costs were $3965 for EA and $3536 for DA (mean difference: $429; P = 0.001, SE $125).Conclusions: Addition of baseline Hb as a variable in propensity score and ESA cost models affects ESA treatment cost estimates in patients with cancer receiving chemotherapy. Cost comparisons based on observational data should use analytical methods that account for differences in clinical variables between treatment groups.

The Impact of Methodological Approach on Cost Findings in Comparison of Epoetin Alfa with Darbepoetin Alfa

Background/Objective: There is interest in longer acting therapies with extended dosing schedules as a mechanism to improve patient compliance and/or decrease health resource utilization (in the case of therapies administered in physician offices/clinics). Based on randomized controlled trial (RCTs) data, the duration of clinical benefit (DCB) of Epoetin alfa (EA) ranges from 2–7 days depending on dose and darbepoetin alfa (DA) ranges from 7–21 days. Comparison of weekly cost between DA and EA in claims data analysis may not be valid if their estimated DCBs are not taken into account. Thus the objective of this study was to use a case study to examine the costs of epoetin alfa (EA) and darbepoetin alfa (DA), 2 erythropoiesis stimulating agents (ESAs), for cancer patients with anemia due to cancer, chemotherapy or radiation treatment.Methods: The MarketScan Research Database, a large national claims database, was used to build EA and DA treatment episodes among patients with a cancer diagnosis on at least 2 medical or facility claims, with no diagnoses indicating chronic renal disease, and with at least 1 EA or DA medical or pharmacy claim. Claims were from patients who were continuously enrolled for benefits during the 6-month period from January-June 2005. Base-case average weekly costs were calculated, with the episode of care (EOC) being the number of days from first date of service for an ESA claim to the last date of service for an ESA claim or until there was a 42-day or longer gap in ESA therapy. Each episode was augmented with an estimated duration of clinical benefit calculated from the last dose administered in the EOC. DCB estimates were based on the results of randomized controlled trials: EA doses <35,000 units =2 days and >=35,000 units =7 days; DA doses <=100 mcg =7 days, 101–299 mcg =14 days, and >=300 mcg =21 days. Cost was reimbursed amount observed in the claims database.Results: Analysis-of-variance (ANOVA) models estimated an adjusted average weekly cost controlling for difference in clinical/demographic differences across EA and DA users. Younger patients, those with more comorbidities, and those with advanced cancer, were found to have increased likelihood of DA use (all P<0.001). After accounting for DCB, the average weekly dose across all episodes was 43,113 units for EA and 94 mcg for DA; the average weekly cost of DA was significantly lower than that of EA ($561 vs. $983, P<0.001). Sensitivity tests on patient selection criteria, length of follow-up period, and definitions of average weekly cost and dose had minimal impact on findings, while changes were more dramatic when different DCB rules were applied. DA had lower costs than EA in all sensitivity analyses except when single dose episodes were excluded and no DCB adjustment was incorporated. With ANOVA adjustment to equalize the population characteristics, estimated average weekly cost was $647 for DA and $833 for EA in the base case..Conclusion: Failure to adjust for differences in patient demographic and clinical characteristics between users of EA and DA can result in misleading comparisons. Cost calculations are sensitive to incorporating the assumption of duration of clinical benefit and the decision to drop and/or retain single dose episodes. To reduce the risk of potential bias, these factors should be taken into account when using retrospective claims data to conduct cost comparisons between agents that have significant differences in dosing schedule.