Prolonged response to recombinant human erythropoietin treatment in patients with myelodysplastic syndrome at a single referral centre in Brazil

OBJECTIVES: To evaluate the effects of epoetin (EPO) alfa treatment on overall survival, event-free survival and response duration in patients with myelodysplastic syndrome (MDS) who were treated at a haematological referral centre in northeastern Brazil. METHODS: This was a retrospective cohort study of 36 patients diagnosed with MDS and treated with EPO alfa at 30,000 to 60,000 IU per week. Clinical data were collected from medical records. The events assessed were non-response to treatment and progression to acute myeloid leukaemia (AML). Statistical analyses were performed using GraphPad Prism 7 and SPSS 24 software. RESULTS: The overall survival of patients who received EPO alfa treatment was 51.64%, with a median of 65 months of treatment, and the overall survival of this group was 100% during the first 24 months. We detected a 43.5-month median event-free survival, with a response rate of 80.5%. We observed responses from 25 to 175 months. Patients with transfusion dependence and those with a high-risk stratification, as determined by the International Prognostic Scoring System (IPSS), the Revised International Prognostic Scoring System (IPSS-R), the WHO classification-based Prognostic Scoring System (WPSS) and the WHO 2016, had a lower event-free survival than other patients. CONCLUSIONS: Despite the wide use of EPO alfa in the treatment of anaemia in patients with MDS, the median response duration is approximately only 24 months. Our data provide encouraging results concerning the benefits of using EPO alfa for the improvement of the quality of life, as patients treated with EPO showed higher overall survival, event-free survival rates and longer response durations than have been previously described in the literature.

Epoetin alfa resistance in hemodialysis patients with chronic kidney disease: a longitudinal study

Anemia is an inevitable complication of hemodialysis, and the primary cause is erythropoietin deficiency. After diagnosis, treatment begins with an erythropoiesis-stimulating agent (ESA). However, some patients remain anemic even after receiving this medication. This study aimed to investigate the factors associated with resistance to recombinant human erythropoietin therapy with epoetin alfa (αEPO). We performed a prospective, longitudinal study of hemodialysis patients receiving treatment with αEPO at our reference hospital from July 2015 to June 2016. Clinical data was collected, and the response to αEPO treatment was evaluated using the erythropoietin resistance index (ERI). The ERI was defined as the weekly weight-adjusted αEPO dose (U/kg per week)/hemoglobin level (g/dL). A longitudinal linear regression model was fitted with random effects to verify the relationships between clinical and laboratory data and ERI. We enrolled 99 patients (average age, 45.7 (±17.6) years; male, 51.5%; 86.8% with hypertension). The ERI showed a significant positive association with serum ferritin and C-reactive protein, percentage interdialytic weight gain, and continuous usage of angiotensin receptor blocker (ARB) hypertension medication. The ERI was negatively associated with serum iron and albumin, age, urea reduction ratio, and body mass index. Our findings indicate that resistance to αEPO was related to a low serum iron reserve, an inflammatory state, poor nutritional status, and continuous usage of ARBs.

Randomized double-blind clinical trial of a new human epoetin versus a commercially available formula for anemia control in patients on hemodialysis

OBJECTIVES: Anemia is a common complication among chronic kidney disease patients on hemodialysis, occurring mostly due to erythropoietin deficiency. This randomized noninferiority trial sought to compare the efficacy and safety of a new epoetin formulation developed by Bio-Manguinhos, a biologics manufacturer affiliated with the Brazilian government, with those of a commercially available product currently used in Brazil (a biosimilar epoetin formulation). METHODS: The sample size needed to enable demonstration of noninferiority with a statistical power of 85% for a between-group difference in hemoglobin levels of no more than 1.5 g/dL was calculated. In total, 74 patients were randomly assigned to receive the epoetin formulation from Bio-Manguinhos (n = 36) or the biosimilar epoetin formulation (n = 38) in a double-blind fashion. The inclusion criteria were current epoetin therapy and stable hemoglobin levels for at least 3 months prior to the study. The primary and secondary outcomes were mean monthly hemoglobin levels and safety, respectively. The dose was calculated according to international criteria and adjusted monthly in both groups according to hemoglobin levels and at the assistant physicians' discretion. Iron storage was estimated at baseline and once monthly. Clinicaltrials.gov: NCT01184495. RESULTS: The study was conducted for 6 months after randomization. The mean baseline hemoglobin levels were 10.9±1.2 and 10.96±1.2 g/dL (p = 0.89) in the Bio-Manguinhos epoetin and biosimilar epoetin groups, respectively. During the study period, there was no significant change in hemoglobin levels in either group (p = 0.055, ANOVA). The epoetin from Bio-Manguinhos was slightly superior in the last 3 months of follow-up. The adverse event profiles of the two formulations were also similar. CONCLUSIONS: The epoetin formulations tested in this study are equivalent in efficacy ...

A randomized crossover study of single biweekly administration of epoetin-alpha compared with darbepoetin-alpha in chronic kidney disease patients not receiving dialysis

BACKGROUND: Recent evidence demonstrates that high doses of epoetin-alpha (EPO-alpha) can be administrated at extended intervals, despite its relatively short serum half-life. However, no prospective randomized trials on the effects of extended dosing intervals of EPO-alpha compared with darbepoetin-alpha (DA-alpha) have been performed. This study was designed to investigate whether a single biweekly (Q2W) administration of a high dose of EPO-alpha is as effective as DA-alpha for anemia in chronic kidney disease (CKD) patients not receiving dialysis. METHODS: Sixty non-dialysis CKD patients were equally randomized to either Q2W subcutaneous EPO-alpha (10,000 unit) or DA-alpha (50microg) therapy groups for the first 6 weeks. After a 6-week washout period, the participants of the EPO-alpha and DA-alpha treatment groups switched to the alternate regimen for 6 weeks. The mean hemoglobin (Hb) levels after erythropoiesis stimulating agent (ESA) therapy and percentage change in Hb levels from baseline to the end of the study were analyzed. RESULTS: The mean Hb levels of postESA therapy increased significantly compared with those of preESA therapy in both ESA regimens. The percentage increase in Hb levels and erythropoietin resistance index did not show a significant difference between the different ESA regimens. No difference was observed between the regimens regarding mean Hb levels after ESA therapy. Additionally, there were no serious adverse effects leading to withdrawal from treatment. CONCLUSION: Biweekly high doses of EPO-alpha therapy may be equally as effective as Q2W DA-alpha therapy in maintaining target Hb levels in non-dialysis CKD patients.

Effects of the administration of erythropoietin-alpha before total knee arthroplasty on patients with mild anemia / 实用医学杂志

Objective To observe the effects of erythropoietin-α administered before the total knee arthroplasty (TKA) on the blood transfusion in patients with mild anemia. Methods 60 patients with mild anemia, who were arranged to receive TKA , from 2010-2012 , were assigned to received either 40 000U of erythropoietin-αfor 3 times (once a week) 3 weeks before the surgery (intervention group, n=30) or not (control group, n=30). Then the hemoglobin levels , transfusion ratio , inpatient length of stay and duration of surgery between the 2 groups were analyzed. Results The hemoglobin level was increased from 11.5 g/dL to 14.3 g/dL in intervention group before the surgery (P<0.01). The blood transfusion rate was decreased from 96.6%to 56.6% (P=0.013) during the surgery. And the length of hospital stay was similar between the 2 groups. Conclusion Erythropoietin-αadministered 3 weeks before the TKA surgery could reduce the blood transfusion rate of patients with mild anemia.

Leukocytoclastic Vasulitis Induced by Methoxy Polyethylene Glycol-Epoetin Beta / 대한피부과학회지

Methoxy polyethylene glycol-epoetin beta (Mircera(R), Roche), a third-generation erythropoiesis-stimulating agent (ESA) is known as a continuous erythropoietin receptor activator (CERA). In patients with anemia associated with chronic kidney disease (CKD), it is administered intravenously or subcutaneously. Treatment-related adverse events induced by methoxy polyethylene glycol-epoetin beta occurred in 6%. Hypertension, diarrhea and nasopharyngitis were the most commonly reported adverse events. Cutaneous adverse reactions are rarely experienced with methoxy polyethylene glycol-epoetin beta including maculopapular eruption, facial erythema, and tinea pedis. To the best of our knowledge, no cases of leukocytoclastic vasculitis associated with methoxy polyethylene glycol-epoetin beta have ever been published in medical literature. Herein, we report on a case of leukocytoclastic vasulitis induced by methoxy polyethylene glycol-epoetin beta in a patient with anemia associated with chronic kidney disease.

Postoperative High-Dose Intravenous Iron Sucrose with Low Dose Erythropoietin Therapy after Total Hip Replacement

Erythropoietin combined with parenteral iron sucrose therapy is an alternative to blood transfusion in anemic patients. It was shown to be effective in surgical patients in several previous studies when used in conjunction with other methods. However, there are no guidelines about safety limits in dosage amounts or intervals. In this study, we report a case of significant postoperative hemorrhage managed with high dose parenteral iron sucrose, low dose erythropoietin, vitamin B12, vitamin C, and folic acid. An 80-year-old female patient presented for severe anemia after a total hip arthroplasty and refused an allogenic blood transfusion as treatment. The preoperative hemoglobin of 12.2 g/dL decreased to 5.3 g/dL postoperatively. She received the aforementioned combination of iron sucrose, erythropoietin, and vitamins. A total of 1,500 mg of intravenous iron sucrose was given postoperatively for 6 consecutive days. Erythropoietin was also administered at 2,000 IU every other day for a total of 12,000 IU. The patient was discharged in good condition on the twelfth postoperative day with a hemoglobin of 8.5 g/dL. Her hemoglobin was at 11.2 g/dL on the twentieth postoperative day.

Comparison of Erythropoietic Effect between Epoetin-alpha and Darbepoetin-alpha in Hemodialysis Patients: A Randomized Crossover Study / 대한신장학회지

PURPOSE: We aim to compare the erythropoietic effects of epoetin-alpha (EA, 4000 IU SC thrice a week) with those of darbepoetin-alpha (DA, 60ug IV weekly, conversion rate to EA=200:1). METHODS: Forty one stable hemodialysis patients were enrolled in this randomized crossover study. After a washout period of erythropoietin stimulating agents (ESA), the patients with hemoglobin (Hb) level of 11.0 g/dL, we stopped ESA. When Hb level decreased to 30% change in EA efficiency relative to DA efficiency. CONCLUSION: There was no significant difference in erythropoietic parameters for both EA and DA.

Therapeutic Effect of Epoetin on Renal Anemia in 45 Cases / 中国药房

OBJECTIVE:To observe the therapeutic effect of epoetin on renal anemia METHODS:45 patients with renal anemia were treated with small dose epoetin subcutaneous injection Using within-patient study,the RBC,Hb,Hct and reticulocyte were measured before and after treatment RESULTS:The RBC,Hb,Hct and reticulocyte count were increased after treatment with epoetin and ARDs were rarely found CONCLUSION:Small dose epoetin subcutaneous injection shows satisfactory therapeutic effect on renal anemia

The Predictive Parameters of Erythropoietin Hyporesponsiveness in Patients on Continuous Ambulatory Peritoneal Dialysis

BACKGROUND: The present study was aimed at investigating the predictive parameters of erythropoietin (epoetin) hyporesponsiveness in patients on continous ambulatory peritoneal dialysis (CAPD). METHODS: We studied 40 patients with end-stage renal disease who had been receiving CAPD for at least 6 months and epoetin therapy for at least more than 2 months. Pearson's simple correlation and multiple stepwise linear regression analysis was used to discover what parameter can predict epoetin resistance. We expressed epoetin resistance index (ERI) as 'weekly epoetin dose/hematocrit/ body weight'. The dose of epoetin is titrated by about 25% every 2 to 4 weeks to maintain a target hematocrit level between 33% and 36%. RESULTS: We analyzed the relationship between ERI and other predictive parameters by Pearson's correlation. These results showed ERI has a statistically significant correlation with transferrin saturation (TS) (r=-0.327, p=0.042), total weekly Kt/Vurea (r=-0.423, p=0.018), serum albumin level (r=-0.458, p= 0.003), normalized protein catabolic rate (nPCR) (r=-0.479, p=0.006), normalized protein equivalent of total nitrogen appearance (nPNA) (r=-0.488, p=0.005) and serum C-reactive protein (CRP) (r=0.332, p=0.036). Regression analysis was performed using stepwise linear regression for multiple variables to discover the most independent variable which is correlated with ERI. ERI was entered as a dependent variable, whereas the other parameters (age, duration of peritoneal dialysis, serum albumin level, CRP, serum ferritin, total weekly Kt/Vurea, nPCR, nPNA, serum iPTH, serum aluminium, TS) were entered as independent variables. This analysis showed CRP is the most significant variable and, if CRP is excluded, nPNA is the significant variable. CRP has a statistically significant correlation with serum albumin level (r=-0.418, p=0.007) and total weekly Kt/Vurea (r=-0.366, p=0.043). High CRP group has more increased level of ERI (p<0.05), age (p<0.05) and serum creatinine level (p<0.05) than normal control, but more decreased level of serum albumin (p<0.01) and serum iron levels (p<0.05). CONCLUSION: These results indicate that CRP is the most important predictor of epoetin hyporesponsiveness.

Recombinant Human Erythropoietin using Preoperative Autologous Donation in Lumbar Stenosis Operations / 대한척추외과학회지

STUDY DESIGN: Prospective randomized clinical trial. OBJECTIVES: To determine the minimal effective pretreatment dosage of recombinant human erythropoietin for preoperative autologous donation in lumbar stenosis surgery. SUMMARY OF LITERATURE REVIEW: Preoperative autologous donation is one of the most widely used methods of autotransfusion. However securing predetermined amount may be difficult due to falling hematocrit with repeated donation especially in patients with low basal hematocrit. In this situation recombinant human erythropoietin(Epoetin alfa) may be used. MATERIALS AND METHODS: Forty five lumbar stenosis patients requiring posterior wide decompression and posterolateral fusion with instrumentation, who had basal hematocrit less than 40% were selected and alloted randomly into 3 groups. Group I(n=15) had pretreatment with Epoetin alfa 50 unit/kg. Group II(n=15) was pretreated with 25 unit/kg. Group III(n=15) had no pretreament. Patients were excluded from donation when their hematocrit values were less than 33%. RESULTS: The mean number of units collected per patient(mean+/-SD) was 3 for group I(P<0.05), 2.84 for group II and 2.67 for the control group. The red cell volumes in pretreated groups(347 ml, 325 ml) were greater than in group III(255 ml, P<0.05). The differences between hematocrits of the first and the third preoperative donations were significantly less in group I(1.50) and group II(1.51) than that of control group(3.73). Two patients in group II and 3 patients in group III required additional homologous transfusion postoperatively. And there were no significant differences in the pattern of postoperative changes of hemoglobin among the groups. There were no significant differences in amount of intraoperative saved blood, postoperative reinfused blood, and postoperative drainage. CONCLUSION: Fifty units/kg of Epoetin alfa seems to be more effective than twenty-five units/kg for preoperative autologous donation in patients requiring posterior wide decompression, posterolateral fusion with instrumentation.