These researchers designed a double-blind, placebo-controlled, multi-center study to examine the effectiveness of epoetin alfa on 56 patients with FRDA. The primary end-point of the study was the effect of epoetin alfa on peak oxygen uptake VO2 max at the cardiopulmonary exercise test. Secondary end-points were frataxin levels in peripheral blood mononuclear cells, improvement in echocardiography findings, vascular reactivity, neurological progression, upper limb dexterity, safety, and quality of life.
A total of 56 patients were randomized; 27 completed the study in the active treatment group, and 26 completed the study in the placebo group [KG1]; VO2 max was not modified after treatment 0.
The 9-hole peg test showed a significant amelioration in the treatment group The treatment was safe and well-tolerated. The authors concluded that although results were not in favor of an effect of epoetin alfa in FRDA, this was the largest study examining its effect.
These investigators stated that it is still possible that epoetin alfa may show some symptomatic effect on upper-limb performance. Aranca and associates noted that FRDA is an inherited, progressive neurodegenerative disease that typically affects teenagers and young adults. Therapeutic strategies and disease insight have expanded rapidly over recent years, leading to hope for the FRDA population.
There is currently no FDA-approved treatment for FRDA, but advances in research of its pathogenesis have led to clinical trials of potential treatments. The authors reviewed emerging therapies and discussed future perspectives, including the need for more precise measures for detecting changes in neurologic symptoms as well as a disease-modifying agent; and EPO is one of the keywords listed in this review.
These researchers treated 35 patients with hairy cell leukemia and compared them with historical controls. The median nadir neutrophil count was roughly 0.
After a median of 10 days of filgrastim, the time for neutrophils to recover to greater than 1. However, these investigators noted no differences with regard to the number of febrile days or hospitalization rates.
The authors concluded that routine use of filgrastim is not recommended. Because the rates of severe anemia from cladribine are low, these investigators similarly do not recommend prophylactic erythropoietin-stimulating agents, although this has never been prospectively studied. Maevis et al. Their review did not recommend epoetin as a therapeutic option. The authors referenced Saven et al.
Zuppa et al investigated a cohort of 14 neonates to compare the effectiveness of recombinant human erythropoietin rHuEPO in two care protocols that differ for doses of rHuEPO administrated and for timing of administration. The authors concluded that their results suggest similar efficacy between the two treatment protocols.
Increasing doses of rHuEPO does not seem to enhance their effectiveness. Donato et al. The neonates were 7 days or older. At start of treatment mean age was Moderate, short-lasting neutropenia, not associated to infections, was observed in 11 patients.
No other adverse effect was observed. They concluded that the administration of erythropoietin appears to be a safe and useful therapy; however, Its efficacy should be confirmed by randomized studies.
Dominquez et al conducted an observational study in 13 newborns with late anemia due to a hemolytic disease caused by Rh isoimmunization 9 cases , ABO isoimmunication 2 cases , glucoseP-dehydrogenase deficiency 1 case or idiopathic 1 case. The newborns began EPO treatment when they reached the haematocrit level for a blood transfusion.
Blood transfusion was not necessary in 11 newborns haematocrit of Significant increases in haemoglobin and reticulocyte figures were seen after EPO treatment. Rath et al. The authors state that treatment of severe anemia with intrauterine red cell transfusions in fetuses with red cell alloimmunization, has led to an increase in perinatal survival, creating a shift towards improving postnatal treatment options. They state that postnatal treatment of anemia consists of top-up transfusions and supplements to support erythropoiesis such as folic acid and iron, and occasionally erythropoietin treatment.
An American Society for Hematology education module uses the reference to Zuppa et al. Bruckl and colleagues examined retrospectively the effectiveness of combined therapy using EPO and erythrocytapheresis EA in patients with hereditary hemochromatosis HH who did not tolerate phlebotomy. A total of 20 patients age range of 43 to 74 years with genetically confirmed HH had received low-dose EPO 4, IU in accordance to the patient's hemoglobin levels between each EA session.
Laboratory parameters including hemoglobin, ferritin, transferrin, and iron were measured at regular intervals. Anemia did not occur in a single patient and no serious adverse events AEs were observed. Combined treatment with EPO and EA was well-tolerated, and all 18 patients who suffered from fatigue prior to therapy recovered.
Median ferritin values were Moreover, they stated that prospective studies comparing this therapeutic option to phlebotomy are needed. Seastone and Gerds stated that MDS are characterized by refractory cytopenias that lead to symptomatic anemia, bleeding, and increased risk for infections. For the past 20 years, the use of darbepoetin and other ESAs to treat symptomatic anemia in lower-risk MDS has been a standard of care. The authors summarized the published experience regarding the use of ESAs, with a special focus on darbepoetin, in patients with MDS and symptomatic anemia.
Huang et al conducted a retrospective study to examine the risk factors for leukemic transformation in patients with primary myelofibrosis. The study that examined clinical variables at the time of diagnosis and specific treatment modalities for their effect on leukemic transformation in patients with primary myelofibrosis PMF who were seen at the Mayo Clinic. In contrast, leukemia-free survival was not found to be affected by a treatment history with hydroxyurea, thalidomide, or other drugs.
The unexpected association between leukemic transformation and a history of treatment with ESA or danazol requires validation by prospective studies. Huang et al discussed ESA having limited therapeutic activity in transfusion-dependent patients with primary myelofibrosis PMF regardless of serum erythropoietin level. The authors reviewed a master database of patients diagnosed with PMF from through , and seen at the Mayo Clinic.
They identified 43 patients median age 67 yrs old treated with ESA. Study inclusion required documentation of a complete blood count prior to therapy and follow-up that was adequate enough to assess response. They excluded patients who were receiving other anemia-improving agents concomitantly with an ESA, such as prednisone, androgens, danazol, or thalidomide. Response was defined as a minimum 2. ESA was administered for a median of 4.
Based on the experience and knowledge of experts in the field, Barbui and colleagues presented a review of critical concepts and developed recommendations on the management of Philadelphia-negative classical myeloproliferative neoplasms.
Key questions were selected according the criterion of clinical relevance. Statements were produced using a Delphi process, and two consensus conferences involving a panel of 21 experts appointed by the European LeukemiaNet ELN were convened. The authors noted a consensus on primary myelofibrosis PMF in that corticosteroids, androgens, erythropoiesis-stimulating agents, and immunomodulators are recommended to treat anemia of PMF; however, all of these agents have limitations, and there are no comparative trials, whereas hydroxyurea is the first-line treatment of PMF-associated splenomegaly.
Hernandez-Boluda et al discussed predictive factors for anemia response to erythropoiesis-stimulating agents ESA in myelofibrosis. The revised criteria of the International Working Group for Myelofibrosis Treatment and Research were used in evaluating anemia response. Median response duration was Over the patient-years of follow-up on ESA treatment, nine patients developed thrombotic complications six arterial, three venous , accounting for 2.
Hernandez-Boluda and colleagues concluded that the data obtained can help to identify which myelofibrosis patients are more likely to benefit from ESA treatment. Rogers and colleagues stated that EPO is neuro-protective in animal models of neonatal hypoxic-ischemic encephalopathy HIE. These researchers previously reported a phase I safety and pharmacokinetic study of EPO in neonates. This article presented the neurodevelopmental follow-up of infants who were enrolled in the phase I clinical trial.
These investigators enrolled 24 newborns with HIE in a dose-escalation study. All infants underwent neonatal brain magnetic resonance imaging MRI reviewed by a single neuro-radiologist.
Outcomes were available for 22 of 24 infants, at mean age of 22 months range of 8 to Moderate-to-severe disability occurred in 1 child 4. All 11 patients with a normal brain MRI had a normal outcome. The authors concluded that this study was the first to describe neurodevelopmental outcomes in infants who received high doses of EPO and TH during the neonatal period. The findings suggested that future studies are needed to evaluate the effectiveness of this new potential neuro-protective therapy.
McAdams and Juul stated that neonatal encephalopathy NE is a major cause of neonatal mortality and morbidity; and TH is standard treatment for newborns at 36 weeks of gestation or greater with intra-partum hypoxia-related NE. Term and late preterm infants with moderate to severe NE show improved survival and neurodevelopmental outcomes at 18 months of age after TH.
Therapeutic hypothermia can increase survival without increasing major disability, rates of an IQ less than 70, or CP. Neonates with severe NE remain at risk of death or severe neurodevelopmental impairment.
The authors discussed the evidence supporting TH and other novel therapeutics for term or near term neonates with NE; EPO is one of the keywords listed in this review. Juul and colleagues noted that HIE remains an important cause of neonatal death and frequently leads to significant long-term disability in survivors.
Therapeutic hypothermia, while beneficial, still leaves many treated infants with lifelong disabilities. Adjunctive therapies are needed, and EPO has the potential to provide additional neuroprotection.
These investigators reviewed the current incidence, mechanism of injury, and sequelae of HIE, and described a new phase-III randomized, placebo-controlled clinical trial of EPO neuro-protection in term and near-term infants with moderate-to-severe HIE treated with therapeutic hypothermia. They presented an overview of HIE, neuro-protective functions of EPO, and the design of a double-blind, placebo-controlled, multi-center clinical trial of high-dose EPO administration, enrolling neonates of greater than or equal to 36 weeks of gestation with moderate or severe HIE diagnosed by clinical criteria.
Diem and associates stated that optic neuritis leads to degeneration of retinal ganglion cells whose axons form the optic nerve. The standard treatment is a methylprednisolone pulse therapy. This treatment slightly shortens the time of recovery but does not prevent neurodegeneration and persistent visual impairment. In a phase II clinical trial performed in preparation of this study, these researchers have shown that EPO protects global retinal nerve fiber layer thickness RNFLT-G in acute optic neuritis; however, the preparatory trial was not powered to show effects on visual function.
The primary objective is to determine the effectiveness of EPO compared to placebo given add-on to methylprednisolone as assessed by measurements of RNFLT-G and low-contrast visual acuity in the affected eye 6 months after randomization.
Inclusion criteria were a first episode of optic neuritis with decreased visual acuity to less than or equal to 0. The most important exclusion criteria were history of optic neuritis or multiple sclerosis or any ocular disease affected or non-affected eye , significant hyperopia, myopia or astigmatism, elevated blood pressure, thrombotic events or malignancy.
After randomization, patients either receive 33, IU rhEPO intravenously for 3 consecutive days or placebo 0. The authors noted that the trial started in September with a planned recruitment period of 30 months.
Cariou and colleagues stated that preliminary data suggested a clinical benefit in treating out-of-hospital cardiac arrest OHCA patients with a high dose of EPO analogs. These researchers performed a multi-center, single-blind, RCT. Patients still comatose after a witnessed OHCA of presumed cardiac origin were eligible.
In the intervention group, patients received 5 intravenous injections spaced 12 hours apart during the first 48 hours 40, units each, resulting in a maximal dose of , total units , started as soon as possible after resuscitation. In the control group, patients received standard care without EPO. The main end-point 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 Secondary end-points included all-cause mortality rate, distribution of patients in CPC levels at different time-points, and side effects.
In total, patients were included in the primary analysis. Baseline characteristics were similar in the 2 groups. At day 60, The mortality rate and proportion of patients in each CPC level did not differ at any time points. The authors concluded that in patients resuscitated from an OHCA of presumed cardiac cause, early administration of EPO plus standard therapy did not confer a benefit, and was associated with a higher complication rate. Messier and Ohls noted that the use of ESAs such as erythropoietin and darbepoetin in preterm and term infants has been studied for over 20 years.
Recent investigations have explored the potential neuroprotective effects of ESAs. These investigators reviewed the recent clinical trials and experimental animal models that provide evidence in support of using ESA to improve the neurodevelopmental outcomes in term and preterm infants. Continued work using animal models have confirmed the neuroprotective properties of ESAs, including promotion of oligodendrocyte development in the face of neuronal injury.
Clinical studies in term and preterm infants have reported the neuroprotective effects following ESA administration, and improved neurodevelopmental outcomes have been reported in the studies of preterm infants. The authors concluded that ESAs show great promise in preventing and treating brain injury in term and preterm infants.
Natalucci and colleagues examined if prophylactic early high-dose recombinant human erythropoietin rhEPO in preterm infants improves neurodevelopmental outcome at 2 years' corrected age. Preterm infants born between 26 weeks 0 days' and 31 weeks 6 days' gestation were enrolled in a randomized, double-blind, placebo-controlled, multi-center trial in Switzerland between and Neurodevelopmental assessments at age 2 years were completed in The minimal clinically important difference between groups was 5 points 0.
Secondary outcomes were motor development assessed with the Psychomotor Development Index , cerebral palsy, hearing or visual impairment, and anthropometric growth parameters.
Among preterm infants randomized mean gestational age of No differences were found between groups in the secondary outcomes. The authors concluded that among very preterm infants who received prophylactic early high-dose rhEPO for neuroprotection, compared with infants who received placebo, there were no statistically significant differences in neurodevelopmental outcomes at 2 years. Moreover, they stated that follow-up for cognitive and physical problems that may not become evident until later in life is required.
In a matched case control study, Talving and co-workers examined if administration of ESA would improve survival following severe traumatic brain injury sTBI.
Each case's controls were chosen to have surgical intensive care unit length of stay more than or equal to the time from admission to first dose of ESA. The primary outcome measure in this study was mortality.
Cases and controls had similar age, gender, mechanisms of injury, incidence of hypotension, Glasgow Coma Scale on admission, Injury Severity Score, and AIS for all body regions.
Although the ESA-treated patients experienced protracted hospital length of stay and comparable surgical intensive care unit free days, they demonstrated a significantly lower in-hospital mortality in comparison to controls at 7. The authors concluded that administration of ESA in sTBI is associated with a significant in-hospital survival advantage without increase in morbidity. They stated that prospective, large, randomized controlled trials are needed to validate these findings.
In a systematic review and meta-analysis, Lee and colleagues examined the effects of EPO on mortality and neurological outcomes in patients with TBI. Electronic databases of studies published up to January 5, were searched to retrieve relevant investigations comparing the outcomes of EPO-treated patients and untreated patients following TBI.
There were no significant differences in the occurrence of complications, such as DVT, between the treatment groups RR However, these researchers stated that the role of EPO in improving neurological outcome s remains unclear, and further well-designed RCTs using modified protocols and involving specific patient populations are needed to clarify this issue, and to verify the findings.
Note : There is a lack of evidence that one brand of erythropoietin alpha i. In addition, there is a lack of reliable evidence that darbepoetin is more effective than erythropoietin alpha or Mircera for darbepoetin's labeled indications.
For persons already receiving either IV or SQ epoetin alfa, the manufacturer recommends the conversion in the following table:. Review History. Clinical Policy Bulletin Notes. Links to various non-Aetna sites are provided for your convenience only.
Aetna Inc. Erythropoiesis Stimulating Agents. Print Share. Acute renal injury Anemia associated only with radiotherapy Anemia associated with chronic obstructive pulmonary disease Anemia due to bleeding other than indications for high-risk surgery e.
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It is also indicated for reduction of allogeneic RBC transfusions in patients undergoing elective, noncardiac, nonvascular surgery. Please refer to the full prescribing information. On October 20, we broke ground on a new location in Portage, MI which represents the first of six upcoming clinical sites in Michigan. Learn More. Have high blood pressure that is not controlled uncontrolled hypertension.
This, in turn, raises your level of hemoglobin, a protein found in red blood cells that carries oxygen to all parts of the body. Increasing your hemoglobin level may lessen the need for a blood transfusion. The rise in hemoglobin does not happen right away. It usually takes 2 to 6 weeks before the number of red blood cells goes up in your body.
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