Epoetin alfa versus darbepoetin alfa in chemotherapy-related anemia

OBJECTIVE: To review and compare the data concerning the clinical activity of epoetin alfa versus darbepoetin alfa when administered to patients with cancer who are experiencing treatment-related anemia. DATA SOURCES: English-language publications from the MEDLINE database (1990-June 2005), published articles, and meeting abstracts were reviewed. STUDY SELECTION AND DATA EXTRACTION: Relevant data were extracted from published reports and abstracts on studies of humans with cancer who developed treatment-related anemia and were treated with epoetin alfa or darbepoetin alfa. DATA SYNTHESIS: Epoetin alfa and darbepoetin alfa are similar agents with identical indications for treatment of anemia in patients with cancer. Clinical trials have demonstrated that both agents can significantly improve hemoglobin levels, reduce transfusion requirements, and improve quality of life. Epoetin alfa is approved for administration at a dose of 150 units/kg subcutaneously 3 times per week, and darbepoetin alfa is approved for administration at a dose of 2.25 units/kg once a week. Clinical studies have demonstrated that epoetin alfa may be administered at 40,000 units once a week and that darbepoetin alfa may be administered at 200 microg every 2 weeks without loss of efficacy. Cost analysis, based on the average wholesale price of each drug alone administered for 12 weeks at Food and Drug Administration-approved doses, revealed that epoetin alfa is less expensive than darbepoetin alfa. When they are administered in the extended schedules, the cost of darbepoetin alfa is slightly less than that of epoetin alfa. However, the total expense associated with the extended schedule of either agent is further reduced by a reduction in other costs associated with drug administration. CONCLUSIONS: Epoetin alfa and darbepoetin alfa have identical indications for treatment of anemia in patients receiving cancer chemotherapy. Clinical trials have demonstrated similar activities with both agents. Darbepoetin alfa, with a longer half-life, can be administered less frequently, saving costs as well as reducing patient office visits.     

Corifollitropin alfa for female infertility

Cardiovascular disease is the leading cause of death in patients with diabetes mellitus. Attempts to improve this statistic tend to focus primarily on the prevention of coronary artery disease. However, coronary artery disease is not the sole cause of cardiac death in diabetic patients; left ventricular dysfunction (LVD) and left ventricular hypertrophy (LVH) are also implicated and, unlike coronary artery disease, are ideal targets for screening. The treatment of left ventricular abnormalities, even when these are asymptomatic, is associated with prognostic benefit. Prescreening diabetic patients with plasma B-type natriuretic peptide (BNP) may permit identification of those who are likely to have left ventricular abnormalities, so that they may be put forward for echocardiography and receive targeted therapy.     

Corifollitropin alfa for female infertility

INTRODUCTION: Follicle-stimulating hormone (FSH) is essential for the development of ovarian follicles. Urinary-derived and recombinant FSH (rFSH) preparations are widely used in infertility treatment but have to be administered daily to achieve steady-state serum levels. Corifollitropin alfa is a hybrid molecule with a prolonged half-life. AREAS COVERED: The development and clinical testing of corifollitropin alfa, including the pharmacodynamics and kinetics, efficacy and drug safety. Searches were performed using the Medline database. EXPERT OPINION: Corifollitropin alfa is composed of the FSH α-subunit and a hybrid of the FSH β-subunit and the C-terminal peptide (CTP) of the human chorionic gonadotropin (hCG) β-subunit. The rationale of developing such a molecule was to reduce patient burden, by reducing the number of injections required to sustain multifollicular growth. Two strengths of corifollitropin are available (for patients ≤ 60 kg and > 60 kg). Compared with a daily dose of 200 IU of rFSH, 150 mcg of corifollitropin is equivalent in safety and pregnancy outcomes in women > 60 and < 90 kg using an antagonist protocol. Another RCT in women ≤ 60 kg also confirmed safety and efficacy of follicular stimulation (100 mcg of corifollitropin versus 150 IU of rFSH), but it was not powered to demonstrate equivalence in terms of pregnancy rates.     

Real-world utilization of andexanet alfa

ObjectiveIn 2018, the FDA approved andexanet alfa for the reversal of life-threatening hemorrhages in patients anticoagulated with apixaban or rivaroxaban. Yet, cost-effective factor Xa inhibitor reversal remains controversial. The objective of this study was to describe real world utilization of andexanet alfa.MethodsThis was a retrospective case series of patients receiving andexanet alfa between July 28, 2018 and April 29, 2019 at a large academic health system. Baseline demographics, anticoagulant type and reversal, as well as brain imaging were collected. Primary endpoints were stability of hematoma for intracranial hemorrhage (ICH), and hemostatic effectiveness for patients undergoing surgical procedures. Secondary endpoints were thromboembolism and 30 day mortality.ResultsOf the 25 patients evaluated, 13 received andexanet alfa for ICH. Eleven of the 13 had follow-up imaging available and stability was observed in 90.9%. Three patients received andexanet alfa for reversal prior to surgical procedures, and 100% hemostatic effectiveness was achieved. Nine patients received andexanet alfa for reversal of extracranial bleeding, including gastrointestinal bleed (n=4). There were no thrombotic events in our cohort, and 30 day mortality was 24%. Sixty-four percent of patients would have met exclusion criteria for the ANNEXA-4 trial.ConclusionThis is the largest series to date describing real-world utilization of andexanet alfa. Our series showed hemostatic efficacy in 90.9% of patients with ICH, and 100% in patients undergoing surgical procedures. There were no thrombotic complications. Yet, larger and comparative studies are needed to clarify the optimal agent and patient selection for reversal of factor Xa inhibitors.     

Use of darbepoetin alfa and epoetin alfa in clinical practice in patients with cancer-related anemia

Background: Patients with cancer may receive erythropoiesis-stimulating agents (ESAs), including darbepoetin alfa (DA) or epoetin alfa (EA), to treat cancer-related anemia (CRA). DA and EA differ, however, with respect to their assumed duration of effect and thus their approved frequency of dosing, complicating direct comparison of their doses and costs. Objective: The objective of this study was to examine, from the perspective of a third-party payer, patterns of use and costs of DA and EA in patients with CRA, using episode-based methodology to account for differences in assumed duration of effect and frequency of dosing with these products. Methods: Using a large US health insurance claims database, we identified all patients with cancer who received ESAs between January 1, 2005, and June 30, 2005 (study period). For each such patient, we identified all unique episodes of care (EOCs) with DA or EA, and then compared mean weekly dose and cost of ESA therapy within these EOCs, which were calculated using the ratio of total dose received and total cost of ESA therapy, respectively, to total EOC duration; only the first EOC for each patient was considered. EOCs were assumed to begin on the date of first ESA admin-istration within the study period, and end on the date of final ESA administration (within the episode) plus an assumed duration of effect based on the ESA received and corresponding dose. We also estimated the ratio of mean weekly dose of EA (in units) to mean weekly dose of DA (in micrograms) (EA/DA weekly dose ratio). Multivariate regression was used to control for differences in baseline characteristics of EA and DA patients. Results: We identified a total of 1226 patients with complete EOCs with ESAs (EA, 381; DA, 845). DA patients were more likely to have had evidence of receipt of chemotherapy (54% vs 47% for EA; P = 0.02); they also had more comorbidities (mean Charlson comorbidity scores, 4.3 and 3.9, respectively; P < 0.01). Estimated mean (95% CI) weekly dose within EOCs was 97 mug (94-99) for DA, and 43,184 U (40,181-46,589) for EA; EA/DA weekly dose ratio was 445:1. Adjustment for differences in patient characteristics yielded a slightly lower ratio (403:1). Results were sen-sitive to the exclusion of EOCs consisting of a single administration of ESA therapy and/or the addition of an assumed duration of effect to the final ESA dose administered. Conclusions: Cost comparisons of DA and EA are sensitive to the assumed duration of effect added to the final dose of ESA therapy, especially for EOCs with relatively few administrations.     

Comparison of effects of darbepoetin alfa and epoetin alfa on serum endothelin level and blood pressure

It is well known that epoetin alfa increases serum endothelin (ET)-1 and blood pressure. No data are available, however, on the effects of darbepoetin alfa on serum ET-1 and blood pressure. This study was conducted to compare the effects of darbepoetin alfa and epoetin alfa on serum ET-1 and blood pressure in patients on hemodialysis (HD). A total of 42 patients on HD were included in the study. Serum samples for measuring levels of ET-1 were taken 30 min after administration of epoetin alfa. After blood samples had been taken from all patients, epoetin alfa was changed to darbepoetin alfa. Three months after the start of darbepoetin alfa treatment, blood samples were taken to measure the same parameters. Mean arterial blood pressure was measured before recombinant human erythropoietin (EPO) administration and 30 min after EPO administration while patients were taking epoetin alfa or darbepoetin alfa. Injection of epoetin alfa or darbepoetin alfa significantly increased serum ET-1 levels compared with levels in those patients who were not on EPO therapy (P < .05). When the effects of epoetin alfa on serum ET-1 level were compared with those of darbepoetin alfa, the 2 types of EPO were found to increase serum ET-1 levels similarly (P > .05). Administration of epoetin alfa or darbepoetin alfa increased systolic and diastolic blood pressures significantly over values in the control group (P < .05). Serum systolic and diastolic blood pressures increased similarly after injection of epoetin alfa or darbepoetin alfa. Administration of darbepoetin alfa increased blood pressure in patients on HD in a way that was positively correlated with enhanced ET-1 release; a similar correlation was noted with epoetin alfa.     

Darbepoetin alfa: a novel erythropoiesis-stimulating protein

OBJECTIVE: To review the pharmacology, pharmacokinetics, clinical efficacy, and safety of darbepoetin alfa. DATA SOURCES: Pertinent references were identified by a MEDLINE search (1995-January 2001) of the medical literature, review of English-language literature and references of these articles, product information, and abstracts from professional meetings. STUDY SELECTION: Clinical efficacy data were gathered from all available trial data citing darbepoetin alfa. Additional information concerning pharmacology, pharmacokinetics, and safety was also reviewed. DATA SYNTHESIS: Darbepoetin alfa is a new erythropoiesis-stimulating protein with a threefold longer half-life than recombinant human erythropoietin (r-HuEPO). Darbepoetin alfa is approved for intravenous and subcutaneous administration in patients requiring and not requiring dialysis. Clinical studies in patients with chronic kidney disease (CKD) have shown darbepoetin alfa to be equivalent to r-HuEPO in terms of increases in hemoglobin concentration, percentage of patients obtaining target hemoglobin, and average time to reach target hemoglobin concentration. Trials are currently ongoing in patients receiving cancer chemotherapy. The adverse event profile appears to be similar between the 2 agents. CONCLUSIONS: The equivalent efficacy and safety profile, as well as the longer half-life, may make darbepoetin alfa an attractive alternative to r-HuEPO in patients with CKD. Since these patients need to receive r-HuEPO 1-3 times weekly at the expense of increased healthcare utilization to improve their hemoglobin, agents such as darbepoetin alfa, with longer durations of action, may reduce healthcare expenses. In addition, enhanced patient compliance may be realized with once-weekly or once every-other-week administration.     

Vascular access thrombosis in epoetin alfa therapy

Correcting anemia in hemodialysis patients may cause an increased incidence of vascular access clotting. Therefore, the incidence of clotting in patients before and during therapy with epoetin alfa was investigated. The records of 45 hemodialysis patients were accessed by computer for data concerning thrombectomy procedures and administration of epoetin alfa during two 13-week periods. Before therapy, 2 out of 45 patients had clotted accesses for a rate of .18 thrombectomy procedures per patient year. During therapy, 7 out of 45 patients had 11 clotted accesses for a rate of 1 thrombectomy procedure per patient year. Clotting incidence was shown to be increased during the epoetin alfa therapy period. The consequences of delaying a dialysis treatment due to a clotted access may be significant and even life-threatening. Both physicians and nurses must have a good understanding of the possible role of epoetin alfa in access thrombosis for patient management.     

Darbepoetin alfa in the treatment of chemotherapy-induced anaemia

Background: Darbepoetin alfa is an erythropoiesis-stimulating agent (ESA), with a longer half-life than previous recombinant human erythropoietins. After its initial development for anaemia due to renal insufficiency, an extensive clinical trial program has defined its role in cancer patients. Objective/methods: Review of the initial registration studies, further development and recent progress, guidelines for use in clinical practice (EORTC, ASCO/ASH), and specific focus on recent safety concerns. Results: Darbepoetin alfa significantly decreases the number of red blood cell transfusions in patients with chemotherapy-induced anaemia, and has been shown to improve health-related quality of life in several studies. The prolonged half-life allows a prolonged dosing interval. Administration every three weeks, a suitable schedule to synchronise with day 1 of many chemotherapy regimens, is as efficient as the initially registered weekly administration. Recent data strongly suggest that the addition of intravenous iron improves haemoglobin response rates. The use of these agents in clinical practice has to be according to the guidelines. Recent safety data reported a negative effect on survival when ESAs were used to treat anaemia that was either not chemotherapy related, or when used to maintain high levels of haemoglobin and prevent anaemia. All of these studies were not in accordance with existing guidelines, while safety data from clinical trials using ESAs according to the guidelines remain reassuring. Conclusion: Darbepoetin alfa has a well defined place in the treatment of chemotherapy-induced anaemia, and is safe when used in line with existing guidelines. Recent safety signals on cancer outcomes in studies not in accordance with these guidelines illustrate the need for further research into the complex interaction between anaemia and tumour hypoxia in cancer patients.     

Use of epoetin alfa in critically ill patients

OBJECTIVE: To discuss the controversies regarding the use of epoetin alfa (EPO) for reducing red blood cell (RBC) transfusions in critically ill patients with anemia. DATA SOURCES: A MEDLINE search (1966-July 2003) was conducted using the search terms anemia; critical illness; erythropoietin; epoetin alfa; and erythropoietin, recombinant. References of selected articles were reviewed for studies that may have been missed by the computerized search. STUDY SELECTION AND DATA EXTRACTION: Studies pertaining to the use of EPO for anemia of critical illness with an emphasis on data obtained from controlled trials. DATA SYNTHESIS: Anemia is a common complication in patients admitted to the intensive care unit (ICU). Two prospective, randomized studies have demonstrated decreased transfusion requirements associated with EPO administration in medical/surgical patients who were in the ICU for at least 3 days and had hematocrit concentrations <38%. No differences were found in length of stay or mortality. A multicenter trial found that a restrictive strategy of RBC transfusion (hemoglobin goal 7-9 g/dL) was associated with in-hospital mortality lower than that with a more liberal approach, which calls into question the 38% hematocrit goal in the EPO trials. Furthermore, preliminary results from an economic analysis of EPO use in the ICU setting have demonstrated that EPO is not cost-effective. CONCLUSIONS: Given the controversies surrounding EPO administration in critically ill patients, institutions are encouraged to develop EPO guidelines to help ensure the most appropriate use of this expensive product. Additional studies regarding patients most likely to benefit from EPO therapy, the most effective dosing regimen, and use of adjunctive therapies are needed.     

Epoetin alfa for predialysis and AZT-treated HIV-positive patients

PROCRIT is an exogenous form of erythropoietin now marketed for use in anemic predialysis patients and AZT-treated HIV-positive patients. It is the same preparation as epogen. It will be up to the physician to determine which form of the drug is prescribed for each patient. Cost issues will probably be a deciding factor as the products are identical. Key differences to keep in mind are that predialysis patients will have to come in to the clinic two or three times a week for injections as they are are not on dialysis and that payment issues could be a problem.