Epoetin Alpha Research Articles

Modern approaches to the treatment of anemia of malignant neoplasms

Anemia in patients with cancer is a common concomitant condition. The development of anemia in cancer has a multifactorial pathogenesis, including inflammation, metastasis of solid tumors to the bone marrow and displacement of normal hematopoiesis sprouts in the bone marrow by tumor cells in hemoblastosis, myelosuppression against the background of chemo/radiation therapy, nutritional insufficiency due to anorexia, etc. Anemia in cancer patients reduces the quality of life, the response to antitumor therapy, increases the risk of tumor progression and is an independent factor negatively affecting survival. The article discusses the tactics of managing patients with anemia in accordance with the Clinical recommendations of the Ministry of Health of the Russian Federation “Anemia in malignant neoplasms” and “Management of CancerAssociated Anemia With Erythropoiesis-Stimulating Agents: ASCO/ASH Clinical Practice Guideline Update”. The results of clinical studies are presented, which indicate the effectiveness of the use of erythropoiesis-stimulating drugs (including epoetin alpha) in oncological practice, which reduce the need for hemotransfusions and increase hemoglobin levels in patients with anemia against the background of antitumor chemotherapy.

MRNA biomarkers sensitive and specific to micro-dose erythropoietin treatment at sea level and altitude.

Recombinant human erythropoietin (rhEPO) is prohibited by the World Anti-Doping Agency. rhEPO abuse can be indirectly detected via the athlete biological passport (ABP). However, altitude exposure challenges interpretation of the ABP. This study investigated whether 5'-aminolevulinate synthase 2 (ALAS2) and carbonic anhydrase 1 (CA1) in capillary dried blood spots (DBSs) are sensitive and specific markers of rhEPO treatment at altitude. ALAS2 and CA1 expression was monitored in DBS collected weekly before, during, and after a 3-week period at sea level or altitude. Participants were randomly assigned to receive 20 IU kg bw-1 epoetin alpha (rhEPO) or placebo injections every second day for 3weeks while staying at sea level (rhEPO, n = 25; placebo, n = 9) or altitude (rhEPO, n = 12; placebo, n = 27). ALAS2 and CA1 expression increased up to 300% and 200%, respectively, upon rhEPO treatment at sea-level and altitude (P-values <0.05). When a blinded investigator interpreted the results, ALAS2 and CA1 expression had a sensitivity of 92%. Altitude did not confound the interpretation. Altitude affected ALAS2 and CA1 expression less than actual ABP markers when compared between sea level and altitude results. An individual athlete passport-like approach simulation confirmed the biomarker potential of ALAS2 and CA1. ALAS2 and CA1 were sensitive and specific biomarkers of micro-dose rhEPO treatment at sea level and altitude. Altitude seemed less a confounding factor for these biomarkers, especially when they are combined. Thus, micro-dose rhEPO injections can be detected in a longitudinal blinded setting using mRNA biomarkers in DBS.

Recombinant erythropoietin in autoimmune hemolytic anemia with inadequate bone marrow response: a prospective analysis

AbstractUp to 30% of patients with autoimmune hemolytic anemia (AIHA) show inadequate bone marrow (BM) compensatory response with inappropriately low levels of reticulocytes and endogenous erythropoietin. Ineffective BM compensation is associated with more severe anemia, transfusion need, and hospital admission, and treatment with recombinant erythropoietin (rEPO) may be beneficial. Here, we prospectively analyzed the efficacy and safety of rEPO in a single-center cohort of 47 patients with AIHA with inadequate reticulocytosis and endogenous erythropoietin at baseline. Epoetin alpha 40 000 international units per week were administered subcutaneously until hemoglobin (Hb) >11 g/dL and then tapered off. Overall response was 55% at 15 days, 74% at 1 month, 74% at 3 months, 80% at 6 months, and 91% at 12 months. Consistently, Hb values significantly increased from baseline to each subsequent time point (P<.001) with a median increase of +1.4, +2.4, +3.4, +3.8, and +4.4 g/dL, respectively. Transfusion needs reduced from 30% to <10% at 15 days and thereafter (P < .001). Concomitant medications included prednisone or methylprednisolone (N = 40, stable since >2 weeks from enrollment), mycophenolate mofetil (N = 1, ongoing since >3 months from enrollment), and rituximab (N = 7 patients with cold agglutinin disease from day 8). No association between concomitant medications and response to rEPO was found. Treatment was generally safe without rEPO-related severe adverse events. The comparison with an AIHA population not treated with rEPO showed a significant benefit of rEPO at 15 days and 1 month on response and Hb increase. These data support the use of rEPO as an add on to standard immunosuppression in AIHA with inadequate BM compensation. This trial was registered at www.clinicaltrials.gov as #NCT05931718.

ВЛИЯНИЕ РОКСАДУСТАТА НА ЭРИТРОПОЭЗ ДИАЛИЗ-ЗАВИСИМЫХ И ДИАЛИЗ-НЕЗАВИСИМЫХ ПАЦИЕНТОВ С ХРОНИЧЕСКОЙ БОЛЕЗНЬЮ ПОЧЕК

Anemia is a common condition in patients suffering from chronic kidney disease. To correct it, a new class of drugs has been developed – prolyl hydroxylase inhibitors. There are able to stimulate the se-cretion of endogenous erythropoietin regardless of oxygen availability, even in patients with end-stage disease. Prolyl hydroxylase is an enzyme that cleaves the alpha subunit of hypoxia-induced factor, which enhances the expression of genes that are responsible for erythropoiesis. Roxadustat is one of the first oral drugs that induce the production of endogenous erythropoietin in patients with renal ane-mia by activating hypoxia-induced factors. Recent results of phase III clinical trials of roxadustat have demonstrated its efficacy and safety. So, for patients who do not need dialysis, roxadustat, compared with placebo, increased the level of hemoglobin by 18.5 g/l, placebo – by 1.3 g/l. In the group of pa-tients on dialysis, the effects of roxadustate and epoetin alpha were compared. The hemoglobin level increased by 12.2 g / l when taking roxadustate, and by 9.9 g / l when taking epoetin. In addition to the main effect, roxadustat also reduced the content of hepcidin, low-density lipoproteins and cholesterol.

Brain Injury Outcomes after Adjuvant Erythropoietin Neuroprotection for Moderate or Severe Neonatal Hypoxic-Ischemic Encephalopathy: A Report from the HEAL Trial

Introduction: Erythropoietin (Epo) is a putative neuroprotective therapy that did not improve overall outcomes in a phase 3 randomized controlled trial for neonates with moderate or severe hypoxic-ischemic encephalopathy (HIE). However, HIE is a heterogeneous disorder, and it remains to be determined whether Epo had beneficial effects on a subset of perinatal brain injuries. Methods: This study was a secondary analysis of neuroimaging data from the High-dose Erythropoietin for Asphyxia and Encephalopathy (HEAL) Trial, which was conducted from 2016 to 2021 at 17 sites involving 23 US academic medical centers. Participants were neonates >36 weeks’ gestation undergoing therapeutic hypothermia for moderate or severe HIE who received 5 doses of study drug (Epoetin alpha 1,000 U/kg/dose) or placebo in the first week of life. Treatment assignment was stratified by trial site and severity of encephalopathy. The primary outcome was the locus, pattern, and acuity of brain injury as determined by three independent readers using a validated HIE Magnetic Resonance Imaging (MRI) scoring system. Results: Of the 500 infants enrolled in HEAL, 470 (94%) had high quality MRI data obtained at a median of 4.9 days of age (IQR: 4.5–5.8). The incidence of injury to the deep gray nuclei, cortex, white matter, brainstem and cerebellum was similar between Epo and placebo groups. Likewise, the distribution of injury patterns was similar between groups. Among infants imaged at less than 8 days (n = 414), 94 (23%) evidenced only acute, 93 (22%) only subacute and 89 (21%) both acute and subacute injuries, with similar distribution across treatment groups. Conclusion: Adjuvant erythropoietin did not reduce the incidence of regional brain injury. Subacute brain injury was more common than previously reported, which has key implications for the development of adjuvant neuroprotective therapies for this population.

Diagnostic and Treatment Challenges in a Pediatric Patient with Progressive Refractory ALPS-like Disease

Introduction: Diagnostic criteria for Autoimmune Lymphoproliferative Syndrome (ALPS) is based on clinical, laboratory and genetic findings. The underlying pathomechanisms are largely related to defects in the lymphocyte apoptosis pathways (FAS, FAS ligand, or CASP10) but other combined immunodeficiencies may also present with ALPS-like features (e.g. CASP8, NFKB1, CTLA4, ALP1). Clinically, patients often present with progressive autoimmune cytopenias and treatment relies on T cell immune modulation. Hereby, we present diagnostic and treatment challenges in a pediatric patient with ALPS-like phenotype with rapid decline during an episode of severe autoimmune hemolytic anemia. MethodsRetrospective chart review for clinical and laboratory data. Deep immune phenotyping was obtained for T, B and NK cells subsets at several timepoints during the acute illness. Genetic evaluation for both germline and somatic mutations were pursued.Case presentation: Patient is an 11-year-old Syrian male of consanguineous parents who presented at age 6 with immune thrombocytopenic purpura (ITP) and met criteria for ALPS with required criteria (chronic lymphadenopathy and increased T Cell Receptor αβ CD4-CD8- double negative T cells (TCRαβDNT) (4.2%, normal <2%), primary accessory criteria (defective lymphocyte apoptosis twice) and secondary accessory criteria (elevated B12, IgG and FAS-L). Panel sequencing (207 genes of inborn errors of immunity) and later Whole Exome Sequencing were both unrevealing. At 11 years of age, he was admitted with a Coombs positive severe autoimmune hemolytic anemia (hemoglobin of 3.5) that was complicated by EBV and parvovirus viremia, and aplastic anemia. Treatment course was complex including steroid, high dose IvIg, rituximab, sirolimus, mycophenolate mofetil, eculizumab, and epoetin alpha. Biomarkers of immune dysregulation, such as TCRαβDNT, follicular helper T cells and CD19hiCD21lo B cells were monitored closely and improved on therapy. Total T cell, CD4, CD8, and Treg populations were all initially low but returned to baseline following combined treatment. Screening for somatic mutations and whole genome sequencing is ongoing. Discussion/ConclusionOur case highlights the diagnostic and treatment challenges in a pediatric patient with ALPS-like Disease. Cellular biomarkers may guide therapy if autoimmune cytopenia recurs. Somatic and germline testing is needed to understand the underpinning of this disorder and may further guide treatment strategies.

Luspatercept in Combination with Recombinant-Erythropoietin in MDS RS Patients: Stimulating Early and Late Erythropoiesis

Myelodysplastic syndrome with ring sideroblasts (MDS RS) and SF3B1 mutation is generally marked by severe anemia, limited response to recombinant erythropoietin (rEPO) and consequent transfusion burden. Recently, luspatercept, a TGF-beta-pathway inhibitor, was shown beneficial in approximately 1/3 of patients by reactivating late-stage erythropoiesis. Since rEPO mainly acts on early-stage erythropoiesis, we hypothesized a possible role of combination therapy in this subset of patients. Seven patients with MDS RS treated with luspatercept in combination with rEPO at two tertiary hematologic centers in Milan, Italy were retrospectively evaluated. Luspatercept was administered according to current data sheet (1 to 1.75mg/kg every 3 weeks). Endogenous (e)EPO was evaluated before rEPO start, and patients with values < 200 IU/L received subcutaneous epoetin alpha 40,000 U/week, while those with higher values received 80,000 U/week. Hematologic data and number of RBC transfusions were collected at each cycle of luspatercept, and hematologic improvement (HI) was assessed according to the revised International Working Group (IWG) 2018. All 7 patients were males, with a median age of 83 years old (70-90). According to IPSS-R, three patients were classified as intermediate risk, while the others were lower risk. At the time of luspatercept start all patients were anemic with median Hb values of 7.3 g/dL (6.1-9.9), while median neutrophil (3.1x103/mm3, 0.8-4.9) and platelet (200x103/mm3,43-282) counts were normal. The median number of RBC units transfused in the last 8 weeks before luspatercept was 8 (3-11). Figure 1 details the timing and doses of luspatercept and rEPO treatment. In total, 5 patients received rEPO as add-on treatment due to non- or loss of response to luspatercept. Median eEPO values in these subjects were 250 (99-445) IU/L. Overall, three patients (Case 1, 2 and 3) achieved HI, and one of them became transfusion independent. Specifically, Case 1 achieved minimal HI with luspatercept after cycles 2 and 6, and lost response; rEPO was added at cycle 12 with HI after cycle 14. Case 2 initially reached HI after cycle 4 but showed several oscillations of pre-transfusion Hb (7 to 9 g/dL). At cycle 13 rEPO was added obtaining HI after cycle 20. Case 3 achieved HI after 2 cycles of luspatercept but lost response after cycle 10; rEPO was added at cycle 14 and he became transfusion independent. Patient 6 had rEPO as a pre-existing therapy and experienced a minimal HI after luspatercept start; rEPO had not been stopped to avoid a drop of pre-transfusion Hb. The other patients did not respond to luspatercept, nor to combination with rEPO, which was added at cycles 14 and 7 (Case 4 and Case 5), or already ongoing at luspatercept start in Case 7. Notably, no treatment emerging adverse events were registered with the combination. In conclusion, despite the small number of cases, these data show for the first time that combination therapy of luspatercept plus rEPO is feasible and beneficial in about one third of subjects. Concomitant stimulation of early and late-stage erythropoiesis may be an interesting strategy that requires further investigation. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

Cost Effectiveness Analysis (CEA) Strategi Terapi Anemia pada Pasien Penyakit Ginjal Kronis

Chronic kidney disease (CKD) is a condition in which the kidneys are unable to maintain a fluid balance of metabolic waste that is progressive, irreversible, and takes place slowly. Anemia is a complication of CKD that contributes to morbidity, mortality, and quality of life of patients, as well as greater costs of care. This study aims to evaluate the differences in the effectiveness and cost of anemia therapy with epoetin in patients with chronic kidney disease. The study was conducted in an analytical-observational manner with a retrospective cohort design from the provider's perspective. The sample used was CKD patients with anemia who met the inclusion criteria for the period January - December 2020, data were taken from medical records and patient financial recapitulation. Statistical analysis was carried out on the effectiveness of anemia therapy with epoetin based on the achievement of clinical outcomes of increasing Hb values within 3 months and financing calculated based on direct medical costs. A total of 113 patients met the inclusion criteria, consisting of 96 patients in the epoetin alpha group and 17 patients in the epoetin beta group. The percentage of achieving therapeutic targets in the epoetin beta group was higher (11.76%) than in the epoetin alfa group (10.42%). The average increase in Hb in the EPO beta group was higher than in the EPO alpha group. The cost of epoetin for anemia treatment in the beta epoetin group (Rp 1,005,365) was lower than the epoetin alfa group (Rp 1,017,188). The ICER value obtained was IDR -125,966, indicating a cost savings of IDR 125,966 to increase 1% of the achievement of therapeutic targets for Hb values &gt;10 g/dl. The cost of therapy with EPO beta is lower than EPO alpha and the achievement of Hb therapy targets is better in EPO beta than EPO alpha.

Epoetin alpha in the treatment of anemia in patients with malignant solid tumors during antitumor drug therapy

Introduction. Erythropoietin (EPO) application is a pathogenetic method for anemia correction in cancer patients.The purpose of study. Clinical evaluation of the efficacy and safety of Eralfon® (epoetin alpha) in treatment for anemia in patients with malignant solid tumors during medical anticancer therapy.Materials and methods. We analyzed the data on anemia treatment with Eralfon® in 184 patients with malignant solid tumors receiving various medical anticancer therapies. Eralfon® was injected subcutaneously 12 000 IU 3 times per week or 40 000 IU once a week. Clinical antianemic effect, the time to maximum antianemic effect, adverse events (AE) were analyzed.Results. Patients were stratified by the grade of anemia, stages of treatment, presence of bone metastases, bleeding, previous medical and radiation anticancer therapies, dosage of Eralfon®. The time to effect was shorter in patients under 65. There were no significant differences in efficacy depending on the dosing regimen of Eralfon®. Efficacy was lower in patients with advanced tumors, especially in bone metastases. A history of tumor bleeding, chemotherapy and/or radiation therapy prolonged the period of hemoglobin recovery to normal values. Arterial hypertension and venous thrombosis were the most common AE associated with Eralfon®. Eralfon® 12 000 IU 3 times per week caused less frequent complications, with no cases of ossealgia and myalgia.Conclusion. Eralfon® demonstrated clinical efficacy in treatment for anemia in patients with solid malignant tumors receiving medical anticancer therapy. Dosage of 12 000 IU 3 times per week provided better control of the antianemic effect and adverse events.

A STUDY ON THE MANAGEMENT OF ANAEMIA IN CHRONIC KIDNEY DISEASE

Anaemia is a common complication for patients with Chronic Kidney Disease and is associated with cardiovascular comorbidities and reduced Quality of Life. Susceptibility may change depending upon the stage of chronic kidney disease, age, and social habits. A Prospective and Observational study was designed to assess the demographics of patients and variables in Anaemia along with the management of Anaemia in Chronic Kidney Disease. The suspected patient’s blood samples were tested for their Haemoglobin, Erythrocyte Sedimentation Rate, and Packed Cell Volume analysed. Among 115 patients, 79 were males, and 36 were females. 58 patients (50.43%) were identified in the age group &gt;60 years due to diabetes, hypertension and other comorbidities. The patients were given Epoetin Alpha (9.6%) and Iron Sucrose (2.3%) along with Ferrous ascorbate and folic acid (2.7%). In 113 patients (98.3%) and 109 patients (94.78%), the Haemoglobin and Packed Cell Volume were increased due to reduced immune response, comorbidity and severity of Chronic Kidney Disease. Non-pharmacotherapy was provided, and the most common was exercise, meditation (25%), Iron-rich food (2.17%) and a renal low salt diet (1.73%). Follow-up was conducted to check the improvement and found that 95.6% of patients recovered.

Blood Count Under the Effect of Erythropoietin (EPO) in Patients with Chronic Hemodialysis

One of the most common associated diseases in dialysis patients is anemia. The number of erythrocytes, hemoglobin and hematocrit is reduced in patients that suffer from anemia. These three measurement parameters represent the most important "red part" of the blood count. Due to renal insufficiency, patients on hemodialysis do not have enough erythropoietin, which healthy kidneys excreted, and is necessary for hematopoiesis. Erythropoietin (EPO) is the main regulator of the daily production of red blood cells. EPO that is execrated by peritubular capillary membrane cells in the kidneys circulates within plasma in order to interact with target cells in the bone marrow to maintain or stimulate erythropoiesis. The main purpose of the action of EPO is the formation of erythroid colonies. During observation of differences in the ordination of EPO in each group between men and women, there is no statistical significance evident in the incidence of anemia before and after therapy, as in p=0.70. The target concentration of hemoglobin, which must be constantly maintained in people with chronic renal anemia, is 110-120 g/l, while the target value of the number of red blood cells is 4-5x10 12/l and the hematocrit value is 0.35-4.5 l/l, with a slight outflow depending on the gender of the patient. The final values of the participants in our study treated with epoetin alpha show higher values of hemoglobin, hematocrit and erythrocytes, while the average values recorded in participants treated with darbepoetin decreased.

Blood Count Under the Effect of Erythropoietin (EPO) in Patients with Chronic Hemodialysis

One of the most common associated diseases in dialysis patients is anemia. The number of erythrocytes, hemoglobin and hematocrit is reduced in patients that suffer from anemia. These three measurement parameters represent the most important "red part" of the blood count. Due to renal insufficiency, patients on hemodialysis do not have enough erythropoietin, which healthy kidneys excreted, and is necessary for hematopoiesis. Erythropoietin (EPO) is the main regulator of the daily production of red blood cells. EPO that is execrated by peritubular capillary membrane cells in the kidneys circulates within plasma in order to interact with target cells in the bone marrow to maintain or stimulate erythropoiesis. The main purpose of the action of EPO is the formation of erythroid colonies. During observation of differences in the ordination of EPO in each group between men and women, there is no statistical significance evident in the incidence of anemia before and after therapy, as in p=0.70. The target concentration of hemoglobin, which must be constantly maintained in people with chronic renal anemia, is 110-120 g/l, while the target value of the number of red blood cells is 4-5x10¹²/l and the hematocrit value is 0.35-4.5 l/l, with a slight outflow depending on the gender of the patient. The final values of the participants in our study treated with epoetin alpha show higher values of hemoglobin, hematocrit and erythrocytes, while the average values recorded in participants treated with darbepoetin decreased.

Comparative effectiveness of erythropoietin alpha and beta in hemodialysis patients: a single-center prospective observational study

ABSTRACT Background and objectives Anemia is a prevalent complication endured by patients with chronic renal disease. Renal anemia also leads to the development of cardio-vascular complications. Epoetin alpha and beta are recombinant human erythropoietin prioritized for managing anemia in hemodialysis patients. The current study aimed to compare the therapeutic efficacy of both erythropoietin alpha and erythropoietin beta in treating renal anemia. Materials and methods This prospective observational study was conducted in a Renal Dialysis Centre at a tertiary care Hospital of Karachi, Pakistan for a period of 3 months. The two erythropoietin products used were human recombinant erythropoietin alpha (Tropin®) and erythropoietin beta (Recormon®). Both groups were age-matched, BMI, eGFR, gender, and comorbidities like diabetes and hypertension were indifferent. The comparative analysis was performed after the completion of 3 months. Results A total of 94 participants were included in the analysis, 54 in group A and 40 in group B. Mean albumin, urea, creatinine, ferritin, iron, and transferrin saturation at inclusion were statistically insignificant, TIBC was higher in group A (p = 0.005) and CRP levels were slightly higher in group B (p = 0.050). There was significant improvement in Hb level (p = 0.025), PCV (p = 0.001), and RBC count (p = 0.007) in group B. While in group A, there was significantly increased MCV (p = 0.005) and MCHC (p = 0.002). In intention to treat analysis, 22.2% of subjects in group A and 40.0% in group B reached desired Hb levels of ≥11 g/l after 3 months. Conclusion In our assessment of hemodialysis patients, erythropoietin beta was found more effective than erythropoietin alpha.

COST-MINIMIZATION ANALYSIS OF USING SHORT AND LONG-ACTING ERYTHROPOESIS-STIMULATING AGENTS FOR CORRECTION OF NEPHROGENIC ANEMIA AGAINST THE BACKGROUND OF SUBSTITUTION THERAPY

Clinical trials conducted in various countries indicate that the use of epoetin alfa in patients with nephrogenic anemia in chronic kidney disease can increase the effectiveness of treatment, reduce the incidence of cardiovascular and infectious complications, and reduce mortality in patients with chronic kidney disease.The aim of the article was to conduct a comparative clinical and economic assessment of the treatment costs of nephrogenic anemia in adult dialysis patients with recombinant human erythropoietins: epoetin alfa, darbepoetin and long-acting methoxy polyethylene glycol – epoetin beta.Materials and methods. The study took into account direct medical costs of nephrogenic anemia pharmacotherapy on the basis of 1 year maintenance therapy according to the following scheme: epoetin alfa – 3 times per week, darbepoetin alfa – once per week, methoxy polyethylene glycol – epoetin beta – once per 2 or 4 weeks. A “costs minimization” analysis was performed for equivalent maintenance epoetins doses for intravenous and subcutaneous administrations. Epoetin alpha equivalents were calculated for an average patient weighing 75 kg by converting a weekly dose of short-acting epoetin (7500 IU) into equivalent doses using dose conversion factors.Results. In the hypothetical cohort of patients under study, epoetin alfa, darbepoetin alfa, and methoxy polyethylene glycol – epoetin beta not differ in effectiveness in achieving target Hb values and in safety. With the equal effectiveness of the investigated drugs, in the studied patients, intravenous epoetin alfa can be less expensive drug therapy relative to the equivalent doses obtained by the calculation: darbepoetin by 14–24% and methoxy polyethylene glycol – epoetin beta by 4–30%. The change-over of patients to the subcutaneous administration makes it possible to decline a weekly dose of epoetin alfa by 20–30% by reducing the frequency of taking the drug to twice a week, and to reduce the cost of drug therapy by a third.Conclusion. Intravenous and subcutaneous administrations of epoetin alfa 2500 IU may be a more economical drug therapy in comparison with the equivalent doses of darbepoetin and methoxy polyethylene glycol – epoetin beta.

Changes in Medicare Part B Spending for Biologic Drugs After Biosimilar Entry Into the Market

This cross-sectional study describes changes in annual Medicare Part B spending for biologic drugs after biosimilar entry, focusing on the first 4 products to experience biosimilar competition: filgrastim, infliximab, epoetin alpha, and pegfilgrastim.

Safety of Marketed Cancer Supportive Care Biosimilars in the US: A Disproportionality Analysis Using the Food and Drug Administration Adverse Event Reporting System (FAERS) Database.

Since the approval and availability of the first biosimilar in 2015 in the United States (US), evidence regarding the post-marketing safety of cancer supportive care biosimilars remains limited. The aim was to explore the adverse event (AE) reporting patterns and detect disproportionate reporting signals for cancer supportive care biosimilars in the US compared to their originator biologics. The US Food and Drug Administration Adverse Event Reporting System database (January 1, 2004-March 31, 2020) was used to identify AE reports for filgrastim, pegfilgrastim, and epoetin alpha by type of product (originator biologics vs. biosimilars) and report characteristics. Plots of AE reports against years were used to reveal the reporting patterns. Disproportionality analyses using reporting odds ratios (RORs) were conducted to detect differences in serious and specific AEs between studied drugs and all other drugs. Breslow-Day tests were used to determine homogeneity between the originator biologic-biosimilar pair RORs for the same AE. Total numbers of AEs for all studied biosimilars increased after marketing. More AE reports were from female patients for all of the studied drugs. More AEs for originator biologics and filgrastim biosimilar were reported by health professionals, while the highest proportion of reports came from consumers for pegfilgrastim and epoetin alpha biosimilars (29% and 44.1%, respectively). Signals of disproportionate reporting in serious AEs were detected for a pegfilgrastim biosimilar (Fulphila®) compared to its originator biologic. Our findings support the similarity in the signals of disproportionate reporting between cancer supportive care originator biologics and biosimilars, except for Fulphila®.

The efficiency and safety of methoxy polyethylene glycol-epoetin beta usage in patients with dialysis, who are transitioning from short-acting epoethins

INTRODUCTION . Methoxy polyethylene glycol-epoetin beta (PEG-EPO) is a representative of a third-generation erythropoiesis-stimulating agent with a continuous erythropoietin receptor activator (CERA). Although the effectiveness of methoxy polyethylene glycol-epoetin beta has been confirmed in multicenter randomized clinical trials, research continues to examine the safety and tolerability in patients with chronic renal anemia previously treated with recombinant human erythropoietins (rhEpo) of the first generation. AIMS . Evaluation of the efficacy and safety during the transition from rhEpo of first generation epoetin alpha (Epocrin, Aeprin, Eralfon) to third generation continuous activator erythropoietin receptor (CERA), methoxy polyethyleneglycol-epoetin beta (Mircera) administered intravenously every 4 weeks to maintain a stable hemoglobin (Hb) in patients with EPO-dependent anemia in programed hemodialysis (PhD). P ATIENTS AND METHODS . A retrospective study was conducted enrolling 116 patients with terminal stage renal failure. They all were undergoing the renal replacement therapy with programmed hemodialysis, and were all being transferred from rhEpo of the first generation (months from -12 to -1) to CERA (Mircera) (months from1 to 12). As rhEpo first generation drugs with epoetin alpha (Alpha-EPO) were used Epocrin, Aeprin, Eralfon. RESULTS . 1. The use of CERA allows one to maintain a stable level of hemoglobin, with smooth dynamics. In sharp contrast, the short-acting epoetins induce drastic fluctuations. 2. The dose modification in the CERA (Mircera) therapy was half as frequent, compared to the frequency of dose modification in the alpha-EPO therapy (1.4±0.15 and 2.1 ± 0.3 episodes/year, respectively). 3. Adverse events associated with the use of CERA (Mircera) were rare. An increase in blood pressure indicators was revealed in CERA (Mircera) therapy, compared with the use of alpha-EPO. CONCLUSION . The use of CERA (Mircera) allows for the effective and safe maintaince of stable hemoglobin level in patients receiving treatment with program hemodialysis.

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 (&amp;lt;95, 95-115, &amp;gt;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&amp;lt;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 &amp;lt;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 &amp;gt;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&amp;lt;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.

Predictors of Response to Erythropoietin in Autoimmune Hemolytic Anemia

Predictors of Response to Erythropoietin in Autoimmune Hemolytic Anemia

Effectiveness and Safety of Switching Originator and Biosimilar Epoetins in Patients with Chronic Kidney Disease in a Large-Scale Italian Cohort Study.

IntroductionReal-world data on the comparative effectiveness and safety of switching among different epoetins (including originators and biosimilars) are limited. In light of current debate about interchangeability, prescribers, some patient groups and decision makers are calling for additional post-marketing evidence on the clinical effects of switching between originator and biosimilar epoetins in chronic kidney disease (CKD) patients.ObjectiveThe objective of this study was to evaluate the effectiveness and safety of switching versus non-switching and of switching from originator/biosimilar epoetin alpha (ESA α) to any other epoetin in CKD patients.MethodsAn observational, record-linkage, multi-database, retrospective cohort study was carried out in four Italian geographical areas. All subjects with at least one ESA α dispensing between 1 January 2009 and 31 December 2015 were retrieved. Switching was defined as any transition between originator/biosimilar ESA α to any other epoetin in a series of two consecutive prescriptions up to 2 years. Switchers were matched 1:1 with non-switchers by baseline propensity score and by duration of ESA α treatment. Switchers and non-switchers were followed up from switching date to a maximum of 1 year. Lack of effectiveness and safety of switching versus non-switching were evaluated through Cox regression models (hazard ratio [HR], 95% confidence interval [CI]). A direct comparison between the two switcher categories (switchers from originator/biosimilar ESA α to any other epoetin) was also performed.ResultsOverall, 14,400 incident users of ESA α for anaemia due to CKD (61.4% originator, 38.6% biosimilar) were available for analysis. During the follow-up, we found no differences on effectiveness (HR 1.02, 95% CI 0.79–1.31 originators; HR 1.16, 95% CI 0.75–1.79 biosimilars) and safety outcomes (HR 1.08, 95% CI 0.77–1.50 originators; HR 1.20, 95% CI 0.66–2.21 biosimilars) between switchers and non-switchers of ESA α. Cumulative probabilities of recording an adverse event, either in terms of lack of effectiveness or safety issue, were the same for two switching categoriesConclusionsIn this large-scale Italian observational multi-database study, switching versus non-switching as well as switching from biosimilar/originator ESA α to any other epoetin in CKD patients is not associated with any effectiveness and safety outcomes.Electronic supplementary materialThe online version of this article (10.1007/s40264-019-00845-y) contains supplementary material, which is available to authorized users.