Erythropoiesis-stimulating Agents In Treatment Research Articles

MO533: Safety of Roxadustat versus Erythropoiesis-Stimulating Agents for Treatment of Anemia in Patients With Chronic Kidney Disease Incident to or not Receiving Dialysis: Pooled Analysis of Four Phase 3 Studies

Abstract BACKGROUND AND AIMS Patients with late-stage chronic kidney disease (CKD) who are non–dialysis-dependent (NDD) or incident to dialysis (ID) (e.g. initiated dialysis within the last 4 months) or dialysis-dependent (DD) represent a vulnerable population at increased risk for morbidity and mortality despite significant clinical advancements in recent years. The safety of roxadustat in patients with NDD or ID-DD CKD requires further elucidation. METHOD In this post-hoc exploratory analysis, safety results from eligible patients with anemia of CKD enrolled in four phase 3, randomized, open-label studies [NDD (DOLOMITES) or ID-DD (SIERRAS, HIMALAYAS, ROCKIES)] were pooled and compared roxadustat to an erythropoiesis-stimulating agent (ESA). Endpoints were time to major adverse cardiovascular event [MACE; myocardial infarction, stroke and all-cause mortality (ACM)] and MACE+ (MACE plus congestive heart failure or unstable angina requiring hospitalization), ACM, and treatment-emergent adverse events (TEAEs). MACE and MACE + were evaluated for non-inferiority using hazard ratios (HRs) at 1.8 and 1.3-upper margins, respectively, and 95% confidence intervals (CIs). TEAEs were descriptively summarized. RESULTS In total, 2142 patients were evaluated (1083 roxadustat; 1059 ESA; 616 NDD; 1526 ID-DD). Roxadustat was non-inferior to ESA for risk of MACE [HR 0.79 (95% CI 0.61–1.02)] and MACE+ [HR 0.78, (95% CI 0.62–0.98)] with a consistent finding for ACM [HR 0.78 (95% CI 0.57–1.05)]. TEAEs were generally comparable between roxadustat and ESA groups, including any TEAE [incidence rate per 100 patient-exposure years (IR/100 PEY) 56.1 versus 53.5], TEAEs leading to discontinuation of study drug (IR/100 PEY 6.7 versus 5.1) and TEAEs leading to death (IR/100 PEY 6.9 versus 7.4). The most frequent (IR/100 PEY) TEAEs were hypertension (roxadustat 12.8, ESA 12.3), end-stage kidney disease (roxadustat 6.6, ESA 6.1), diarrhea (roxadustat 7.1, ESA 4.8) and hyperkalemia (roxadustat 4.3, ESA 4.8). CONCLUSION There was no evidence of an increased risk of cardiovascular events or mortality with roxadustat compared with ESA in patients with anemia who have NDD or ID-DD CKD. Although TEAE development occurred commonly in both the roxadustat and ESA groups, patients infrequently discontinued a study drug because of an adverse event.

A prospective observational study on the effect of Erythropoiesis stimulating agents in chronic kidney disease Anemia patients

Background and Objectives: Anemia is a frequent complication, and significant morbidity and mortality in patient with chronic kidney disease (CKD). Erythropoiesis Stimulating Agents (ESAs) have become the standard care for anemia t erapy and reduces need for blood transfusions. The bjective of the study was to evaluate the safety and effect of ESAs and to create the awareness among patients regarding the Erythropoiesis stimulating agents through patient i formation leaflets. Methods: The prospective observational study of 6-month duration was conducted in a tertiary care hospital. A total of 162 patients on ESAs were enrolled in the study. Patients were followed for continuously and the mean difference is assessed by monitoring the primary and secondary hematological parameters before and after ESAs administration. Patient information leaflet was given t the patients for education and awareness about ESAs. Results: Out of 162 patients, after the administration of ESAs mean value increase in hemoglobin level was found from base line 6.9g/dL to 11.6g/dL. Significant improvement was noted in CKD anemia patient indicating impact of patient counseli g. Conclusion: It can be concluded that Erythropoiesis Stimulating Agents in treatment of anemia along with effective counseling from clinical pharmacist benefits CKD patients and improves the health outcomes.

Methoxy Polyethylene Glycol-Epoetin Beta as a Novel Erythropoiesis Stimulating Agent with Possible Nephroprotective and Cardiovascular Protective Effects in Non-Dialysis Chronic Kidney Disease Patients.

Chronic kidney disease (CKD) is an important health problem, because of unsuccessful outcomes such as CKD progression to end stage renal disease and high risk of cardiovascular disease (CVD). Anemia, associated with CKD, is considered a non-traditional risk factor for CVD which may contribute to faster CKD progression. Anemia treatment with erythropoiesis-stimulating agents (ESAs) seems to exert non-hematopoietic effects on different tissues and organs, including cardiovascular system and kidneys. On the other hand, clinical use of high doses of short-acting ESAs and higher target hemoglobin level were associated with higher risk of CVD. Literature data indicate the usefulness of long-acting ESAs in treatment of anemia in non-dialysis CKD patients. In particular, continuous erythropoietin receptor activator seems to be a good choice in these patients because of its efficiency, safety and monthly administration. Continuous but slower erythropoietin receptor activation, using methoxy polyethylene glycol-epoetin beta (MPG-EPO), administered once a month, slowly corrects anemia without exceeding the recommended hemoglobin level. An overview of the available literature may suggest nephroprotective and cardiovascular protective effects of MPG-EPO. It seems possible that anemia treatment with a novel ESAs, MPG-EPO in early stages of CKD may reduce CVD risk in these patients and delay CKD progression. This review of available literature evaluates the correlation between continuous erythropoietin receptor activation using MPG-EPO and CKD progression and CVD risk in non-dialysis CKD patients.

Future Directions in Management of Anemia in Heart Failure

Anemia in patients with heart failure (HF) may be caused by several factors, including hemodilution, iron or erythropoietin deficiency, and chronic kidney disease. Published pilot studies of erythropoiesis-stimulating agents (ESAs) and intravenous iron therapy in anemic heart failure patients demonstrate improvement in surrogate markers of functional capacity and quality of life, and reasonable safety profile during short-term use. However, the long-term safety of ESA in treatment of anemia in patients with HF remains a concern due to documented harmful side effects of ESA in anemic patients with advanced chronic kidney disease and cancer. Ongoing prospective clinical outcomes studies of ESA and intravenous iron therapies will provide important data that may pave the way for new avenues in the treatment of anemia in the future.