Comparative pharmacoeconomic analysis of the use of erythropoiesis-stimulating drugs for the treatment of anemia in cancer patients

Introduction. Currently, a number of pharmacoeconomic studies describing use of erythropoietin stimulating agent (ESA) in cancer patients with anemia have been published, however, most of the publications on this topic are foreign. At the same time, there are practically no studies comparing the economic efficiency of various ESA preparations with each other. Some of works by foreign colleagues reflect that the clinical efficacy of using ESA namely the degree of increase in Hb, significantly depends on the patient’s body weight: the higher the weight, the greater the dose of EPO is required for a single administration and a course of therapy.Aim. Сomparative pharmacoeconomic analysis of epoetin alfa usage for the treatment of anemia in adult cancer patients with weight 80 kg.Materials and methods. The following drugs were selected for comparative analysis: epoetin alfa, epoetin beta, darbepoetin. Clinical efficacy was assessed in terms of the rate of in Hb level increase. Pharmacoeconomic analysis was carried out using the cost-effectiveness method (CEA).Results. Тhe usage of epoetin alfa 12,000 IU for 8 weeks therapy course in cancer patients weighting over 80 kg had a better cost-effectiveness ratio compared to epoetin alfa (10,000 IU, 30,000 IU, 40,000 IU) and darbepoetin, giving way in price only to the cheapest epoetin beta which can be administered 4 injections simultaneously. Its the infringement of patients rights to avoid additional pain. Its the infringement of patients rights to avoid additional pain. At the 16th week of therapy, the usage of epoetin alfa 12,000 IU had an advantage over all ESA.Conclusions. Тhe usage of russian epoetin alfa 12,000 IU for the treatment of anemia in adult cancer patients weighing over 80 kg approximately in real clinical practice in Russian Federation is an economically justified approach to the medical care organization.

Comparative Efficacy and Safety Study of Darbepoetin Alfa versus Epoetin Alfa in Management of Anemia Associated with ESRD in Egyptian Hemodialysis Patients

Background: Anemia is one of the most common complications of Chronic Kidney Disease (CKD). The vast majority of Egyptian CKD patients are interchangeably treated with Darbepoetin Alfa (DPA) and Epoetin Alfa (EPA) to achieve and maintain target hemoglobin levels. Our study aimed to compare the efficacy and safety of DPA versus EPA for managing anemia amongst Egyptian patients with CKD undergoing dialysis. Methods: A multicenter, open label, randomized, prospective, parallel study was conducted. Patients with CKD undergoing dialysis with Hb level <10 g/dl were enrolled. The primary efficacy endpoint was the change in hemoglobin concentration at the evaluation period (weeks 20-24). Pre-specified adverse events of interest following administration, including blood transfusions requirement, blood pressure and hemoglobin excursions, the relationship between C - Reactive Protein (CRP) and hemoglobin, were assessed. Findings:: Only 98 of 104 enrolled patients completed the study, fifty patients received EPA, and 48 patients received DPA. Our results showed that a significantly higher percentage of patients who achieved target Hb level ≥ 11 g/dL in DPA treated group vs. EPA as well as the meantime to achieve Hb level ≥ 10 g/dL was shorter in DPA treated group. Safety profiles of both treatments were similar. A negative correlation was observed between serum CRP and hemoglobin level in hemodialysis patients. Conclusion: Our study showed that DPA was more effective and well tolerated in achieving and maintaining Hb levels with lower dosing frequency compared to EPA. Furthermore, CRP is recommended to be routinely measured where patients with higher CRP require high ESA doses.

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.

Posterior Ischemic Optic Neuropathy after Cervical Spine Surgery

Purpose: To describe a patient with posterior ischemic optic neuropathy (PION) after cervical spine surgery who recovered after treatment.Case summary: A 51-year-old woman presented with eye pain and decreased visual acuity in the left eye, which had begun 8 hours after cervical spine surgery in the prone position. Her best-corrected visual acuity (BCVA) was 20/20 in the right eye and hand motion in the left eye; a relative afferent pupillary defect was present in the left eye. Ductions and versions were normal with pain in the left eye. The results of slit lamp examination, fundoscopic examination, fluorescein angiography, and optical coherence tomography were unremarkable in both eyes. Brain and orbital magnetic resonance imaging showed no abnormal findings in the visual pathway, such as brain infarction or intracranial artery stenosis. The patient was diagnosed with PION in the left eye. Because postoperative anemia had developed with a rapid decrease in hemoglobin from 14.7 g/dL to 9.9 g/dL, red blood cell (RBC) transfusion was performed together with intravenous high-dose steroid therapy and subcutaneous epoetin alfa injection. After 3 weeks, the patient’s BCVA improved to 20/22 in the left eye.Conclusions: Unilateral PION developed after cervical spine surgery in the prone position. Visual improvement was observed after RBC transfusion, intravenous high-steroid therapy, and subcutaneous epoetin alfa injection.

Myelodysplastic Syndrome with Excess of Blasts - Long Term Partial Remission with Low Dose Prednisone, G-CSF and Epoetin Alfa

We have used low-dose prednisone, in conjunction with granulocyte, colony-stimulating factor (G-CSF) and erythropoietin, to treat an elderly patient with myelodysplastic syndrome (MDS) with an excess of blasts. Our findings indicate that such treatment is safe and may be effective in the long term survival of patients with high-risk MDS.

FC 071ENHANCED DEGRADATION OF 3-HYDROXY-3-METHYLGLUTARYL COENZYME A REDUCTASE (HMGCR) MAY CONTRIBUTE TO THE LOWERING OF LDL CHOLESTEROL SEEN WITH ROXADUSTAT IN CHRONIC KIDNEY DISEASE PATIENTS WITH ANEMIA

Background and Aims Roxadustat is an oral hypoxia-inducible factor prolyl hydroxylase (HIF-PH) inhibitor approved in China and Japan for the treatment of anemia in patients with chronic kidney disease (CKD). In Phase 3 clinical studies, roxadustat was shown to increase hemoglobin levels in both dialysis-dependent (DD) and non-dialysis-dependent (NDD) CKD patients with anemia. This increase in hemoglobin and the accompanying decrease in hepcidin, a hormone that sequesters iron in intracellular stores, is consistent with the known role that HIF plays in the regulation of erythropoiesis. The HIF pathway may also influence cholesterol metabolism; at high altitude, total and low-density lipoprotein cholesterol (LDL-C) decrease in healthy individuals. The cholesterol biosynthesis pathway is well characterized and 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMGCR) has long been recognized as the rate-limiting enzyme. Multiple feedback mechanisms are known to regulate HMGCR activity, one of which involves degradation of HMGCR via interaction with insulin-induced genes 1 and 2 (INSIG1 and INSIG2), two closely related endoplasmic reticulum membrane proteins. Here, we report clinical trial data showing a reduction in LDL-C in patients with anemia of CKD who were treated with roxadustat, and describe the results of investigation into the mechanism of this cholesterol-lowering effect. Method We studied the effect of roxadustat on LDL-C levels in human subjects and examined the potential underlying mechanisms via cell culture experiments. Clinical data were pooled from six pivotal phase 3 studies, three in patients with NDD-CKD and three in patients with DD-CKD, including those with incident dialysis (ID; on dialysis &lt;4 months at randomization). Mean changes from baseline (CFB) in LDL-C (regardless of statin use) averaged over weeks 12–28 were analyzed using a mixed ANCOVA model of repeated measures. We investigated the effect of roxadustat on HMGCR activity in a cell-free enzyme assay and on HMGCR protein levels in cultured Hep3B cells. We explored involvement of the HIF pathway in regulation of HMGCR protein levels in Hep3B cells by means of HIF-1α/HIF-2α small interfering (si)RNA knockdown. Protein expression levels were assessed by SDS-PAGE and Western blot analysis or electrochemiluminescent immunoassays. Gene expression levels were evaluated by real-time quantitative reverse-transcriptase polymerase chain reaction (RT-PCR). Results In patients with NDD-CKD, there was a 17.2% reduction in LDL-C averaged over weeks 12–28 in the roxadustat group (n=1994) vs. a 1.4% increase in the placebo group (n=1430) (least-squares mean [LSM] [SE] treatment difference = -19.83 mg/dL [1.186], p&lt;0.0001) (Table). In patients with DD-CKD, LDL-C was reduced by 18.5% in the roxadustat group (n=1650) vs. 1.7% in the epoetin alfa group (n=1741) (LSM treatment difference = -15.80 mg/dL, p&lt;0.0001) (Table). In the ID-DD patients, LDL-C dropped by 21.5% in the roxadustat group (n=680) vs. 4.6% in the epoetin alfa group (n=691) (LSM treatment difference = -17.50 mg/dL, p&lt;0.0001) (Table). After confirming that roxadustat does not directly inhibit HMGCR enzyme activity, we found that the increase in HMGCR protein levels caused by cholesterol depletion in cells was suppressed by roxadustat. However, roxadustat had no effect on HMGCR mRNA expression, indicating that the suppression of HMGCR protein levels by roxadustat was the result of an effect on protein turnover. Subsequent siRNA studies revealed that the regulation of HMGCR protein levels by roxadustat was HIF dependent and mediated via upregulation of INSIG2. Conclusion These data show that treatment with roxadustat vs. placebo or epoetin alfa lowered LDL-C in patients with NDD-CKD and DD-CKD, respectively, and highlight a potential HIF-dependent mechanism for this cholesterol-lowering effect.