Background: New erythropoiesis-stimulating agents (ESAs) with a longer half-life have been developed for the treatment of anemia as a complication of patients with end-stage renal disease. Objectives: The objective of...Background: New erythropoiesis-stimulating agents (ESAs) with a longer half-life have been developed for the treatment of anemia as a complication of patients with end-stage renal disease. Objectives: The objective of the present study was to assess the hemoglobin (Hb) stability of a Japanese cohort of hemodialysis (HD) patients who were simultaneously switched from darbepoetin alfa (DA) to epoetin beta pegol (CERA). Methods: This was an observational, prospective study of HD patients 20 years of age or more who were switched from intravenous (IV) DA to IV CERA and continued on HD for at least 3 months. The dose was adjusted to maintain the Hb level to within 1.0 g/dl of the baseline value. Results: A total of 68 HD patients (75.0% male, median age 63.0 years) were enrolled. The patients’ mean Hb levels were 10.8 ± (0.6) g/dl at Month 0, 10.9 ± 0.7 at Month 1, 10.8 ± 0.7 at Month 2, and 10.9 ± 0.8 at Month 3, and the differences from the level at Month 0 were not significant. After the switch, the ESA dose decreased significantly (P P < 0.0001). Conclusion: Switching from DA to CERA was associated with approximate 89% reduction of the required dose in Japanese HD patients being treated with an ESA and showed a favorable impact on the treatment of renal anemia, including the need for less frequent injections and a reduction of the ESA dose.展开更多
Objective: Long-acting darbepoetin-α (DA) has recently been used to treat renal anemia in patients with chronic renal failure. It is considered clinically useful because its duration of action is longer than that of ...Objective: Long-acting darbepoetin-α (DA) has recently been used to treat renal anemia in patients with chronic renal failure. It is considered clinically useful because its duration of action is longer than that of conventional epoetin-α. In this study, we investigated changes in the levels of the oxidative stress marker malondialdehyde-modified low density lipoprotein (MDA-LDL), renal anemia, and renal function when patients were treated for chronic renal failure switched from epoetin-α to DA. Materials and Methods: The subjects included nine patients with chronic renal failure and renal anemia who were treated with epoetin-α on an outpatient basis at our department. Blood was sampled prior to the switch and at 3, 6, and 12 months after the switch. We then investigated changes in MDA-LDL, hemoglobin (Hb), and creatinine (Cr) levels. Results: There were no significant changes in MDA-LDL and Hb levels after switching to DA. A significant increase was observed in Cr levels after 12 months compared with those prior to switching. Conclusion: Once-a-month administration of DA did not result in an increase in oxidative stress, and therefore, DA is considered capable of controlling renal anemia.展开更多
Aim: This observational clinical study tested the effect of injection frequency of the biosimilar epoetin zeta on the weekly dose needed to maintain stable hemoglobin levels in chronic kidney diseases (CKD) patients o...Aim: This observational clinical study tested the effect of injection frequency of the biosimilar epoetin zeta on the weekly dose needed to maintain stable hemoglobin levels in chronic kidney diseases (CKD) patients on intermittent high-flux hemodialysis (HD). Patients and Methods: CKD patients (n = 33) on regular HD therapy 3 times a week were treated for 18 months with epoetin zeta i.v. The hemoglobin levels, the weekly dose as well as the injection frequency of epoetin zeta were monitored at least every two weeks. Patients were followed in three time periods: 1) extended follow-up (months 1 - 18);2) intervention phase (months 19 - 21);and 3) post intervention observation phase (months 28 - 30). During extended follow-up the majority of patients (n = 21) received only one injection of epoetin zeta per week. During the intervention phase, injection frequency was increased to 3 injections per week in all patients accompanied by a reduction in weekly doses of approximately 20% - 30%. Following a 9 month period of dose adjustment all parameters were monitored again in the post-intervention phase. Results: During the first 18 months of epoetin zeta therapy the mean hemoglobin level was stable between 11 and 12 g/dl. The mean weekly dose of epoetin zeta was 7939 IU/week in month 6 and 7909 IU/week in month 18 (p = not significant). The mean frequency (injections/week) was 1.27 in month 6 and 1.29 in month 18 (not significant). Compared to month 18, at the end of the observation at month 30, hemoglobin levels were stable, mean injection frequency increased to 2.25 (p < 0.001) and the mean weekly dose decreased to 5469 IU/week (-31.7%, p < 0.001). Conclusions: Increasing the injection frequency of the short acting biosimilar epoetin zeta to two to three injections per week reduces the weekly dose and thereby the costs of ESA therapy of renal anemia significantly.展开更多
Background:This study was to explore the clinical efficacy and safety of darbepoetin alfa injection replacing epoetin alfa injection(recombinant human erythropoietin injection,rHuEPO)for the treatment of anemia associ...Background:This study was to explore the clinical efficacy and safety of darbepoetin alfa injection replacing epoetin alfa injection(recombinant human erythropoietin injection,rHuEPO)for the treatment of anemia associated with chronic kidney failure in Chinese patients undergoing hemodialysis.Method:This study was a multicenter,randomized,open-label,intergroup parallel control phase III noninferiority trial from April 19,2013 to September 9,2014 at 25 sites.In this study,the members of the darbepoetin alfa group underwent intravenous administration once per week or once every two weeks.The members of the control drug epoetin alfa group underwent intravenous administration two or three times per week.All subjects underwent epoetin alfa administration during the 8-week baseline period.After that,subjects were randomly assigned to the darbepoetin alfa group or epoetin alfa group.The noninferiority in the changes of the average Hb concentrations from the baseline to the end of the evaluation period(noninferiority threshold:-1.0 g/dl)was tested between the two treatments.The time-dependent hemoglobin(Hb)concentration and the maintenance rate of the target Hb concentration(the proportion of subjects with Hb concentrations between 10.0 and 12.0 g/dl)were also evaluated.Iron metabolism,including changes in the serum iron,total iron-binding capacity,ferritin,transferrin saturation,and comparisons of the dose adjustments between the two groups during the treatment period were analyzed further.Adverse events(AEs)were also observed and compared,and the safety was analyzed between the two treatment groups.The conversion rate switching from epoetin alfa to darbepoetin alfa was also discussed.SAS?software version 9.2 was used to perform all statistical analyses.Descriptive statistics were used for all efficacy,safety,and demographic variable analyses,including for the primary efficacy indicators.Results:Four hundred and sixty-six patients were enrolled in this study,and ultimately 384 cases were analyzed for safety,including 267 cases in the darbepoetin alfa group and 117 cases in the epoetin alfa group.There were 211 cases in the per-protocol set,including 152 cases in the darbepoetin alfa group and 59 cases in the epoetin alfa group.The changes in the average Hb concentrations from the baseline to the end of the evaluation period were-0.07 and-0.15 g/dl in the darbepoetin alfa group and epoetin alfa group respectively.The difference between the two groups was 0.08 g/dl(95%confidence interval[CI]:-0.22 to 0.39),and the lower limit of the 95%CI was-0.22>-1.0 g/dl.The average Hb concentrations of the two groups were 10.88-11.43 g/dl(darbepoetin alfa)and 10.91-11.38 g/dl(epoetin alfa)during the study period of Weeks 0-28,with the maintenance rates of the target Hb concentration ranging within 71%-87%and 78%-95%in the darbepoetin alfa group and epoetin alfa group respectively.During the period of comparison between the two groups,the incidence of AEs in the darbepoetin alfa group was 61.42%,while in the epoetin alfa group it was 56.41%.All of the adverse events and reactions in the study were those commonly associated with hemodialysis.Conclusion:The overall efficacy and safety of darbepoetin alfa for the treatment of Chinese renal anemia patients undergoing hemodialysis are consistent with those of epoetin alfa.展开更多
BACKGROUND Hema-Plus,a recombinant human erythropoietin(rHuEPO)or epoetin alfa has shown effectiveness in correction of anemia in Thai population in clinical practice.This study was aimed to demonstrate efficacy and s...BACKGROUND Hema-Plus,a recombinant human erythropoietin(rHuEPO)or epoetin alfa has shown effectiveness in correction of anemia in Thai population in clinical practice.This study was aimed to demonstrate efficacy and safety under the evidencebased approach.AIM To evaluate the efficacy and safety of rHuEPO(Hema-Plus)for treatment of anemia over 12 wk in Thai patients with Stage V chronic kidney disease(CKD)on peritoneal dialysis(PD).METHODS This study was an open-label,multi-center study to enroll 30 CKD patients identified to start PD with hemoglobin(Hb)less than 9.5 g/dL,serum ferritin more than 100 ng/mL,serum transferrin saturation more than or equal to 20%and who had not previously received epoetin.Patients with conditions that could increase the risk of adverse effects from study participation or interfere with study outcomes,were using concomitant androgens or had secondary hyperparathyroidism were excluded.All eligible patients started Hema-Plus by SC injection at 4000 IU once or twice weekly(week 0)and with follow-up at weeks 2,4,8,and 12.Dosage adjustment could be done to achieve Hb level of 11-12 g/dL.Primary end point was mean change in Hb level from baseline to end of treatment(week 12).Safety was assessed throughout the study.Quality of life(QoL)was assessed using KDQOL-36.RESULTS All 30 enrolled patients completed the study.Mean(standard deviation)Hb at baseline(week 0)to the end of 12 wk was significantly increased from 7.39(1.29)g/dL to 11.15(1.73)g/dL(paired t-test,P value<0.001).Overall change of Hb means from baseline over the other 4 visits was statistically significantly increased(repeated measure ANOVA,P value<0.001).Ten out of 39 adverse events(AEs)were serious.Two serious AEs were probably related to study medication by investigators’assessment.At week 12,the QoL scores in all domains were significantly increased from baseline.CONCLUSION Hema-Plus administered for 12 wk for treatment of anemia in patients on PD effectively increased Hb levels with acceptable safety profile.展开更多
Anemia in chronic kidney disease (CKD) is common, causing morbidity and mortality, and is primarily due to reduced erythropoietin (EPO) release and, to a lesser degree, shortened red cell survival. Erythropoietin Stim...Anemia in chronic kidney disease (CKD) is common, causing morbidity and mortality, and is primarily due to reduced erythropoietin (EPO) release and, to a lesser degree, shortened red cell survival. Erythropoietin Stimulating Agents like epoetin Alfa and darbepoetin alpha are used commonly to treat this form of anemia. Recent evidence suggests increased morbidity and mortality associated with higher hemoglobin in the setting of these agents use. Whether these complications are due to higher dose of erythropoietin or its resistance (i.e. inflammation), or achieving a higher hemoglobin remains unclear. Tightening restrictions on these agents has led to increase interest in the use of non-ESA adjuvants to improve erythropoiesis. This review will highlight the most promising of these agents.展开更多
英国药品和健康产品管理局（MHRA）警告倍他依泊汀（Epoetin Beta）用于早产儿，尤其是用于胎龄小于31周，出生体重不足1.25 kg 的早产儿时可能增加视网膜病变的风险，相应的“产品特征概要”将进行修订以纳入可能的视网膜病变风险。MH...英国药品和健康产品管理局（MHRA）警告倍他依泊汀（Epoetin Beta）用于早产儿，尤其是用于胎龄小于31周，出生体重不足1.25 kg 的早产儿时可能增加视网膜病变的风险，相应的“产品特征概要”将进行修订以纳入可能的视网膜病变风险。MHRA 警告使用倍他依泊汀预防新生儿贫血时，应该权衡获益和风险，包括可能的视网膜病风险，监测新生儿视网膜病的特征，以及建议家长或者护理人员仔细监测婴儿眼睛的任何疾病迹象。展开更多
文摘Background: New erythropoiesis-stimulating agents (ESAs) with a longer half-life have been developed for the treatment of anemia as a complication of patients with end-stage renal disease. Objectives: The objective of the present study was to assess the hemoglobin (Hb) stability of a Japanese cohort of hemodialysis (HD) patients who were simultaneously switched from darbepoetin alfa (DA) to epoetin beta pegol (CERA). Methods: This was an observational, prospective study of HD patients 20 years of age or more who were switched from intravenous (IV) DA to IV CERA and continued on HD for at least 3 months. The dose was adjusted to maintain the Hb level to within 1.0 g/dl of the baseline value. Results: A total of 68 HD patients (75.0% male, median age 63.0 years) were enrolled. The patients’ mean Hb levels were 10.8 ± (0.6) g/dl at Month 0, 10.9 ± 0.7 at Month 1, 10.8 ± 0.7 at Month 2, and 10.9 ± 0.8 at Month 3, and the differences from the level at Month 0 were not significant. After the switch, the ESA dose decreased significantly (P P < 0.0001). Conclusion: Switching from DA to CERA was associated with approximate 89% reduction of the required dose in Japanese HD patients being treated with an ESA and showed a favorable impact on the treatment of renal anemia, including the need for less frequent injections and a reduction of the ESA dose.
文摘Objective: Long-acting darbepoetin-α (DA) has recently been used to treat renal anemia in patients with chronic renal failure. It is considered clinically useful because its duration of action is longer than that of conventional epoetin-α. In this study, we investigated changes in the levels of the oxidative stress marker malondialdehyde-modified low density lipoprotein (MDA-LDL), renal anemia, and renal function when patients were treated for chronic renal failure switched from epoetin-α to DA. Materials and Methods: The subjects included nine patients with chronic renal failure and renal anemia who were treated with epoetin-α on an outpatient basis at our department. Blood was sampled prior to the switch and at 3, 6, and 12 months after the switch. We then investigated changes in MDA-LDL, hemoglobin (Hb), and creatinine (Cr) levels. Results: There were no significant changes in MDA-LDL and Hb levels after switching to DA. A significant increase was observed in Cr levels after 12 months compared with those prior to switching. Conclusion: Once-a-month administration of DA did not result in an increase in oxidative stress, and therefore, DA is considered capable of controlling renal anemia.
文摘Aim: This observational clinical study tested the effect of injection frequency of the biosimilar epoetin zeta on the weekly dose needed to maintain stable hemoglobin levels in chronic kidney diseases (CKD) patients on intermittent high-flux hemodialysis (HD). Patients and Methods: CKD patients (n = 33) on regular HD therapy 3 times a week were treated for 18 months with epoetin zeta i.v. The hemoglobin levels, the weekly dose as well as the injection frequency of epoetin zeta were monitored at least every two weeks. Patients were followed in three time periods: 1) extended follow-up (months 1 - 18);2) intervention phase (months 19 - 21);and 3) post intervention observation phase (months 28 - 30). During extended follow-up the majority of patients (n = 21) received only one injection of epoetin zeta per week. During the intervention phase, injection frequency was increased to 3 injections per week in all patients accompanied by a reduction in weekly doses of approximately 20% - 30%. Following a 9 month period of dose adjustment all parameters were monitored again in the post-intervention phase. Results: During the first 18 months of epoetin zeta therapy the mean hemoglobin level was stable between 11 and 12 g/dl. The mean weekly dose of epoetin zeta was 7939 IU/week in month 6 and 7909 IU/week in month 18 (p = not significant). The mean frequency (injections/week) was 1.27 in month 6 and 1.29 in month 18 (not significant). Compared to month 18, at the end of the observation at month 30, hemoglobin levels were stable, mean injection frequency increased to 2.25 (p < 0.001) and the mean weekly dose decreased to 5469 IU/week (-31.7%, p < 0.001). Conclusions: Increasing the injection frequency of the short acting biosimilar epoetin zeta to two to three injections per week reduces the weekly dose and thereby the costs of ESA therapy of renal anemia significantly.
文摘Background:This study was to explore the clinical efficacy and safety of darbepoetin alfa injection replacing epoetin alfa injection(recombinant human erythropoietin injection,rHuEPO)for the treatment of anemia associated with chronic kidney failure in Chinese patients undergoing hemodialysis.Method:This study was a multicenter,randomized,open-label,intergroup parallel control phase III noninferiority trial from April 19,2013 to September 9,2014 at 25 sites.In this study,the members of the darbepoetin alfa group underwent intravenous administration once per week or once every two weeks.The members of the control drug epoetin alfa group underwent intravenous administration two or three times per week.All subjects underwent epoetin alfa administration during the 8-week baseline period.After that,subjects were randomly assigned to the darbepoetin alfa group or epoetin alfa group.The noninferiority in the changes of the average Hb concentrations from the baseline to the end of the evaluation period(noninferiority threshold:-1.0 g/dl)was tested between the two treatments.The time-dependent hemoglobin(Hb)concentration and the maintenance rate of the target Hb concentration(the proportion of subjects with Hb concentrations between 10.0 and 12.0 g/dl)were also evaluated.Iron metabolism,including changes in the serum iron,total iron-binding capacity,ferritin,transferrin saturation,and comparisons of the dose adjustments between the two groups during the treatment period were analyzed further.Adverse events(AEs)were also observed and compared,and the safety was analyzed between the two treatment groups.The conversion rate switching from epoetin alfa to darbepoetin alfa was also discussed.SAS?software version 9.2 was used to perform all statistical analyses.Descriptive statistics were used for all efficacy,safety,and demographic variable analyses,including for the primary efficacy indicators.Results:Four hundred and sixty-six patients were enrolled in this study,and ultimately 384 cases were analyzed for safety,including 267 cases in the darbepoetin alfa group and 117 cases in the epoetin alfa group.There were 211 cases in the per-protocol set,including 152 cases in the darbepoetin alfa group and 59 cases in the epoetin alfa group.The changes in the average Hb concentrations from the baseline to the end of the evaluation period were-0.07 and-0.15 g/dl in the darbepoetin alfa group and epoetin alfa group respectively.The difference between the two groups was 0.08 g/dl(95%confidence interval[CI]:-0.22 to 0.39),and the lower limit of the 95%CI was-0.22>-1.0 g/dl.The average Hb concentrations of the two groups were 10.88-11.43 g/dl(darbepoetin alfa)and 10.91-11.38 g/dl(epoetin alfa)during the study period of Weeks 0-28,with the maintenance rates of the target Hb concentration ranging within 71%-87%and 78%-95%in the darbepoetin alfa group and epoetin alfa group respectively.During the period of comparison between the two groups,the incidence of AEs in the darbepoetin alfa group was 61.42%,while in the epoetin alfa group it was 56.41%.All of the adverse events and reactions in the study were those commonly associated with hemodialysis.Conclusion:The overall efficacy and safety of darbepoetin alfa for the treatment of Chinese renal anemia patients undergoing hemodialysis are consistent with those of epoetin alfa.
基金the Ethics Committee,Institute for the Development of Human Research Protections(IHRP),No.IHRP 2365/2556The Ethics Committee of Udon Thani Hospital,No.8/2559and Siriraj Institutional Review Board Faculty of Medicine Siriraj Hospital,Mahidol University,No.Si 588/2016.
文摘BACKGROUND Hema-Plus,a recombinant human erythropoietin(rHuEPO)or epoetin alfa has shown effectiveness in correction of anemia in Thai population in clinical practice.This study was aimed to demonstrate efficacy and safety under the evidencebased approach.AIM To evaluate the efficacy and safety of rHuEPO(Hema-Plus)for treatment of anemia over 12 wk in Thai patients with Stage V chronic kidney disease(CKD)on peritoneal dialysis(PD).METHODS This study was an open-label,multi-center study to enroll 30 CKD patients identified to start PD with hemoglobin(Hb)less than 9.5 g/dL,serum ferritin more than 100 ng/mL,serum transferrin saturation more than or equal to 20%and who had not previously received epoetin.Patients with conditions that could increase the risk of adverse effects from study participation or interfere with study outcomes,were using concomitant androgens or had secondary hyperparathyroidism were excluded.All eligible patients started Hema-Plus by SC injection at 4000 IU once or twice weekly(week 0)and with follow-up at weeks 2,4,8,and 12.Dosage adjustment could be done to achieve Hb level of 11-12 g/dL.Primary end point was mean change in Hb level from baseline to end of treatment(week 12).Safety was assessed throughout the study.Quality of life(QoL)was assessed using KDQOL-36.RESULTS All 30 enrolled patients completed the study.Mean(standard deviation)Hb at baseline(week 0)to the end of 12 wk was significantly increased from 7.39(1.29)g/dL to 11.15(1.73)g/dL(paired t-test,P value<0.001).Overall change of Hb means from baseline over the other 4 visits was statistically significantly increased(repeated measure ANOVA,P value<0.001).Ten out of 39 adverse events(AEs)were serious.Two serious AEs were probably related to study medication by investigators’assessment.At week 12,the QoL scores in all domains were significantly increased from baseline.CONCLUSION Hema-Plus administered for 12 wk for treatment of anemia in patients on PD effectively increased Hb levels with acceptable safety profile.
文摘Anemia in chronic kidney disease (CKD) is common, causing morbidity and mortality, and is primarily due to reduced erythropoietin (EPO) release and, to a lesser degree, shortened red cell survival. Erythropoietin Stimulating Agents like epoetin Alfa and darbepoetin alpha are used commonly to treat this form of anemia. Recent evidence suggests increased morbidity and mortality associated with higher hemoglobin in the setting of these agents use. Whether these complications are due to higher dose of erythropoietin or its resistance (i.e. inflammation), or achieving a higher hemoglobin remains unclear. Tightening restrictions on these agents has led to increase interest in the use of non-ESA adjuvants to improve erythropoiesis. This review will highlight the most promising of these agents.
文摘英国药品和健康产品管理局（MHRA）警告倍他依泊汀（Epoetin Beta）用于早产儿，尤其是用于胎龄小于31周，出生体重不足1.25 kg 的早产儿时可能增加视网膜病变的风险，相应的“产品特征概要”将进行修订以纳入可能的视网膜病变风险。MHRA 警告使用倍他依泊汀预防新生儿贫血时，应该权衡获益和风险，包括可能的视网膜病风险，监测新生儿视网膜病的特征，以及建议家长或者护理人员仔细监测婴儿眼睛的任何疾病迹象。
