-
Pharmacology Research & Perspectives Aug 2020The attainment of target hemoglobin levels in hemodialysis patients is low. Several factors play a role, such as hyporesponsiveness to erythropoiesis-stimulating agents... (Randomized Controlled Trial)
Randomized Controlled Trial
The attainment of target hemoglobin levels in hemodialysis patients is low. Several factors play a role, such as hyporesponsiveness to erythropoiesis-stimulating agents (ESA), but also suboptimal prescribing of ESA and iron. The goal of this study was to investigate if a pharmacist-managed dosing algorithm for darbepoetin alfa (DA) and iron sucrose improves the attainment of target hemoglobin levels. In this randomized controlled trial, 200 hemodialysis patients from a Dutch teaching hospital were included. In the intervention group (n = 100), a pharmacist monthly provided dose recommendations for DA and iron sucrose based on dosing algorithms. The control group (n = 100) received usual care. In the intervention group, the percentage per patient within the target range (PTR) for hemoglobin (target range 6.8-7.4 mmol/L) and iron status was higher than in the control group (for hemoglobin median 38.5% vs 23.1%, P = .001 and for iron status median 21.1% vs 8.3%, P = .003). The percentage of high hemoglobin levels (>8.1 mmol/L) was lower in the intervention group (median 0.0% vs 7.7%, P = .034). The weekly dose of DA was lower in the intervention group (median 34.0 vs 46.9 mcg, P = .020), whereas iron dose was higher (median 75 vs 0 mg). No difference was found for the percentage of hemoglobin levels below the target range. In conclusion, a pharmacist-managed dosing algorithm for DA and iron sucrose increased the attainment of target levels for hemoglobin and iron status, reduced the percentage of high hemoglobin levels, and was associated with a lower DA and a higher iron sucrose dose.
Topics: Adult; Aged; Aged, 80 and over; Algorithms; Darbepoetin alfa; Dose-Response Relationship, Drug; Female; Ferric Oxide, Saccharated; Hematinics; Hemoglobins; Hospitals, Teaching; Humans; Male; Middle Aged; Netherlands; Pharmacists; Pharmacy Service, Hospital; Professional Role; Renal Dialysis; Young Adult
PubMed: 32715653
DOI: 10.1002/prp2.628 -
CEN Case Reports Nov 2022Hypoxia-inducible factor prolyl hydroxylase inhibitors improve anemia in CKD and dialysis patients and were approved for anemia treatment with these populations in...
Hypoxia-inducible factor prolyl hydroxylase inhibitors improve anemia in CKD and dialysis patients and were approved for anemia treatment with these populations in Japan. An 89 year-old man with anemia and on maintenance hemodialysis was successfully treated with a dose-up of darbepoetin alfa from 10 to 20 μg per week, and the dose was gradually tapered to 5 μg. Later, serum hemoglobin levels decreased with the newly occurring sustained inflammation and left pleural effusion of an unknown cause, and the darbepoetin alfa dose was increased again to 20 μg per week, which was not effective. Darbepoetin alfa was switched to 4 mg of daprodustat daily, which was fairly effective under sustained inflammation, with serum hemoglobin levels maintained at 11-12 g/dL. The increase in hemoglobin levels was ascribed to the increase in the number of red blood cells, not the mean corpuscular hemoglobin level. During the inflammatory state, despite the contrasting effect on anemia by the 20 μg of darbepoetin alfa weekly and 4 mg of daprodustat daily, the reticulocyte counts were equivalent. The serum erythropoietin levels during daprodustat administration were within the physiological range (8.5-18.8 mIU/mL). For anemia treatment in hemodialysis patients, daprodustat is less influenced by the inflammatory status than darbepoetin alfa, and one of the possible reasons for this includes the extended red blood cell lifespan.
Topics: Male; Humans; Aged, 80 and over; Darbepoetin alfa; Renal Dialysis; Erythropoietin; Hemoglobins; Treatment Outcome; Anemia; Inflammation
PubMed: 35534679
DOI: 10.1007/s13730-022-00706-1 -
The Journal of Pediatric Pharmacology... 2023This study is to evaluate the effects of darbepoetin alfa (darbe) on neutrophil count in preterm neonates treated for anemia of prematurity.
OBJECTIVE
This study is to evaluate the effects of darbepoetin alfa (darbe) on neutrophil count in preterm neonates treated for anemia of prematurity.
METHODS
This was a retrospective chart review comparing the absolute neutrophil counts (ANCs) of neonates administered 2 doses of subcutaneous darbe 10 mcg/kg to that of a randomly selected comparator group of neonates not administered the drug. Neonates <34 weeks gestational age, gestational age between 23w1d and 33w4d, born between July 2016 and June 2019, were included in the study.
RESULTS
The ANCs of 45 darbe-treated neonates compared with those of 45 randomly selected comparator control neonates revealed no difference in the rate of occurrence of neutropenia (ANC ≤1000/μL) between the darbe-treated neonates (26.7%) and comparator neonates (24.4%) (p > 0.99). There was also no difference in the rate of occurrence of severe neutropenia (ANC ≤500/μL) between the darbe-treated neonates (11.1%) and comparator neonates (6.7%) (p = 0.70). Darbepoetin alfa did not lead to differences in rates of resolution of neutropenia or severe neutropenia.
CONCLUSIONS
Short-term administration of darbe did not affect the ANCs of preterm neonates treated for anemia of prematurity. There was no difference in the rates of occurrence of neutropenia, severe neutropenia, or resolution of either between the darbe-treated neonates and comparator neonates.
PubMed: 36777988
DOI: 10.5863/1551-6776-28.1.41 -
Journal of Managed Care & Specialty... Sep 2021Because health plans each issue their own policies, drug coverage can vary. This variation can result in patients having unequal access to treatment. In this study, we...
Because health plans each issue their own policies, drug coverage can vary. This variation can result in patients having unequal access to treatment. In this study, we evaluate commercial health plans' coverage policies for erythropoiesis-stimulating agents (ESAs) for patients with anemia resulting from chronic kidney disease (CKD). To assess how a set of US commercial health plans cover ESAs for patients with anemia due to CKD. Our second objective was to examine the evidence that the plans reviewed when formulating their coverage policies. We used the Tufts Medical Center Specialty Drug and Evidence and Coverage Database to identify coverage policies issued by 17 of the largest US commercial health plans for ESAs. The following drugs were indicated for anemia due to CKD: darbepoetin alfa, methoxy polyethylene glycol-epoetin beta, epoetin alfa (available as two brands), and epoetin alfa-epbx. Coverage policies were current as of May 2019. We determined whether the health plans applied any restrictions, such as step therapy protocols or patient subgroup restrictions, in their coverage policies. We categorized the evidence that plans cited to support their policies into seven categories: randomized controlled trials (RCTs), real-world evidence (RWE) studies (studies based on data collected in a real-world setting), other clinical studies (eg, single arm trials), systematic reviews and/or meta-analyses, clinical or treatment guidelines, health technology assessments, and economic evaluations. We categorized 72.5% of coverage policies (58/80 policies) as equivalent to the FDA label and 27.5% (22/80 policies) as more restrictive. In restricted policies, plans most often applied step therapy protocols (18/22 policies), followed by prescriber requirements (4/22 policies), and patient subgroup restrictions (3/22 policies). Five health plans applied restrictions in at least half of their coverage policies; seven plans did not apply restrictions in any policy. Plans that cited evidence reviewed an average of 10 citations across their ESA coverage policies, ranging from one to 29 studies. Plans varied with respect to the types of cited studies: at least 50% of evidence cited by five health plans was RCTs, while half or more of the evidence cited by four health plans was clinical or treatment guidelines. Health plans varied in how they covered ESAs for patients with anemia due to CKD and in the evidence cited in their coverage policies. Inconsistencies in plans' coverage policies may have implications for patients' access to ESAs. This study was funded by Otsuka Pharmaceutical Development and Commercialization. Sanon, Redmond, and Mogahadam are employed by Otsuka Pharmaceutical. Michalopoulos was employed by Otsuka Pharmaceutical at the time of this study. Margaretos, Panzer, and Chambers are employed by Tufts Medical Center, Institute for Clinical Research and Health Policy Studies, Center for the Evaluation of Value and Risk in Health. Lai was with Tufts Medical Center, Institute for Clinical Research and Health Policy Studies, Center for the Evaluation of Value and Risk in Health at the time of this study.
Topics: Anemia; Hematinics; Insurance Coverage; Insurance, Health; Organizational Policy; Renal Insufficiency, Chronic
PubMed: 34464213
DOI: 10.18553/jmcp.2021.27.9.1221 -
Cureus Dec 2020Background and objective Anemia is a common prognosis of chronic kidney disease (CKD). It is predominantly managed with synthetic erythropoietin. The principal objective...
Background and objective Anemia is a common prognosis of chronic kidney disease (CKD). It is predominantly managed with synthetic erythropoietin. The principal objective of this study was to compare the cost-effectiveness of the use of short-acting erythropoietin with the long-acting one to maintain serum hemoglobin (Hb) concentration within the range of 10.5-12 g/dL. Method This was a retrospective cohort study involving patients diagnosed with stage 5 CKD according to the Saudi Society of Nephrology and Transplantation conducted at eight tertiary care centers in the Tabuk region, Saudi Arabia. We compared the cost-effectiveness of long-acting erythropoietin with the short-acting one. The decision analysis model and Markov model were established to simulate a cohort of 55-year-old patients to estimate the incremental cost and quality-adjusted life-year (QALY) for chronic hemodialysis patients (CHP) treated with either darbepoetin-alfa or epoetin-beta for at least nine months. The incremental cost per QALY was the main outcome marker for using both medications. Serum HB levels were monitored on a monthly basis and costs were calculated. Results A total of 291 CHP met our inclusion criteria; 194 of them were treated with darbepoetin-alfa while 97 were treated with epoetin-beta. The mean age was 56.3 ± 11.2 years for the darbepoetin-alfa group and 55.2 ± 7.8 years for the epoetin-beta cohort. The baseline serum Hb was 10.68 ± 0.98 g/dL for darbepoetin-alfa patients and 11.63 ± 0.32 g/dL for the epoetin-beta group (p=0.003). We observed a significant difference between the percentage of patients successfully treated with epoetin-beta and those managed with darbepoetin-alfa (80.4% vs. 63.92%, p=0.01) with considerably less cardiovascular side effects. The average annual cost per patient was estimated at $919.47 and $12,319.41 for epoetin-beta and darbepoetin-alfa respectively. Also, the average effectiveness was 0.58 for darbepoetin-alfa vs. 0.61 for epoetin-beta. The average cost-effectiveness ratio was $980.25 and $15,023.66 with an incremental cost difference of -$966 in favor of epoetin-beta compared to darbepoetin-alfa. Conclusion Based on our findings, treating anemia in hemodialysis patients using epoetin-beta is very cost-effective compared to managing them with darbepoetin-alfa.
PubMed: 33415047
DOI: 10.7759/cureus.11895 -
Therapeutic Apheresis and Dialysis :... Apr 2020The aim of this study was to compare the efficacy and safety of intravenous JR-131, a darbepoetin alfa biosimilar, to darbepoetin alfa in hemodialysis patients with... (Comparative Study)
Comparative Study Randomized Controlled Trial
The aim of this study was to compare the efficacy and safety of intravenous JR-131, a darbepoetin alfa biosimilar, to darbepoetin alfa in hemodialysis patients with renal anemia. In this 24-week, multicenter, randomized, double-blinded, parallel-group phase 3 study, 334 hemodialysis patients with renal anemia who had been receiving darbepoetin alfa were randomized to either JR-131 or darbepoetin alfa group. The initial dose was set based on the darbepoetin alfa dose during the observation period. The primary endpoint was change in hemoglobin level from baseline to end of treatment. The 95% confidence interval of the difference in the change in hemoglobin level between the groups was -0.19 to -0.20 g/dL, within the equivalent margin of -0.5 to 0.5 g/dL. No notable treatment-emergent adverse events were observed in either group. JR-131 was therapeutically equivalent to darbepoetin alfa, and the safety profile of JR-131 was similar to that of darbepoetin alfa.
Topics: Adult; Aged; Aged, 80 and over; Anemia; Biosimilar Pharmaceuticals; Darbepoetin alfa; Double-Blind Method; Female; Hematinics; Humans; Male; Middle Aged; Renal Dialysis; Renal Insufficiency, Chronic
PubMed: 31325212
DOI: 10.1111/1744-9987.13422 -
Cureus Jan 2024Anemia is a prevalent and debilitating complication in patients with chronic kidney disease (CKD). It presents multifaceted challenges that impact patients' quality of... (Review)
Review
Anemia is a prevalent and debilitating complication in patients with chronic kidney disease (CKD). It presents multifaceted challenges that impact patients' quality of life and overall well-being. The advent of darbepoetin alfa (DPO) as a therapeutic alternative to recombinant human erythropoietin alpha (EPO) has revolutionized the management of CKD-associated anemia. This review article presents a comprehensive comparative analysis highlighting the advantages of DPO over EPO in the effective management of anemia, in both predialysis and dialysis-dependent (DD) CKD patients. DPO's distinct pharmacokinetic advantages play a pivotal role in its efficacy and safety. With a significantly longer half-life and several-fold increased biological activity compared to EPO, DPO enables extended dosing intervals. Through an in-depth examination of diverse clinical trials, it becomes evident that DPO consistently demonstrates remarkable efficacy and safety in improving and maintaining hemoglobin (Hb) levels. Furthermore, its simplified dosage regimen, coupled with the convenience of less frequent administration, not only improves patient adherence but also translates to reduced healthcare costs and resource utilization. In conclusion, this review provides compelling evidence of the advantages of DPO over conventional recombinant human EPO for managing anemia in CKD patients, both in the predialysis and dialysis-dependent CKD patients. DPO's pharmacokinetic advantages, patient-centered advantages, enhanced compliance, and cost-effectiveness converge to establish DPO as a transformative therapeutic option. In both predialysis and dialysis settings, DPO's superior efficacy and patient-centric attributes collectively redefine the landscape of anemia management in CKD.
PubMed: 38313992
DOI: 10.7759/cureus.51613 -
PloS One 2021Hypoxia-inducible factor (HIF) prolyl hydroxylase domain inhibitors, which have recently become clinically available for treating renal anemia, are attracting attention...
Hypoxia-inducible factor prolyl hydroxylase domain inhibitor may maintain hemoglobin synthesis at lower serum ferritin and transferrin saturation levels than darbepoetin alfa.
BACKGROUND
Hypoxia-inducible factor (HIF) prolyl hydroxylase domain inhibitors, which have recently become clinically available for treating renal anemia, are attracting attention for their novel mechanisms of action.
METHODS
Relationships of reticulocyte hemoglobin content (CHr), which reflects recent Hb synthesis, with serum ferritin (s-ft) and transferrin saturation (TSAT) were examined in 30 patients on hemodialysis after switching from darbepoetin alfa (DA) to roxadustat (Rox). Iron deficiency was defined as CHr < 32.0 pg. Cutoff values of s-ft and TSAT were determined using receiver operating characteristic curves for the endpoint CHr ≥ 32.0 pg. Logistic analysis was performed with the reference group having s-ft or TSAT below the corresponding cutoff value (low vs high).
RESULTS
With the endpoint CHr ≥ 32.0 pg on Day 0, cutoff values for s-ft and TSAT were respectively 49.7 ng/mL and 21.6% on Day 0 and 35.5 ng/mL and 16.2% on Day 28. With the endpoint CHr ≥ 32.0 pg on Day 28, cutoff values for s-ft and TSAT on Day 0 were 81.6 ng/mL and 23.9%, respectively. According to multivariable logistic analysis, the odds ratios of CHr ≥ 32.0 pg on Day 0 were significantly higher for high TSAT on Day 0 [34.7 (95% CI 2.42-131.0), p<0.003] and Day 28 [24.8 (95% CI 2.75-224.0), p = 0.004]. There were no significant differences by s-ft. Odd ratios of CHr ≥ 32.0 pg on Day 28 were also significantly higher for high s-ft on Day 0 [16.0 (95% CI 1.57-163.0), p = 0.019] and high TSAT on Day 0 [13.5 (95% CI 1.24-147.0), p<0.033].
CONCLUSIONS
Our results suggest Hb synthesis was maintained with lower TSAT and s-ft during Rox therapy compared with DA therapy. To avoid iron deficiency during the 4 weeks after switching DA to Rox, ideal s-ft and TSAT levels before the switch are 81.6 ng/mL and 23.9%, respectively.
Topics: Aged; Darbepoetin alfa; Female; Ferritins; Hemoglobins; Hepcidins; Humans; Hypoxia-Inducible Factor-Proline Dioxygenases; Male; Middle Aged; Prolyl-Hydroxylase Inhibitors; Transferrin
PubMed: 34143801
DOI: 10.1371/journal.pone.0252439 -
Kidney Research and Clinical Practice May 2024For anemia management in patients with chronic kidney disease not on dialysis, darbepoetin alfa (DA), which has a shorter half-life but is more inexpensive than...
Efficacy and cost-effectiveness of darbepoetin alfa once every 4 weeks versus continuous erythropoietin receptor activator once every 4 weeks for anemia correction in patients with chronic kidney disease not on dialysis.
BACKGROUND
For anemia management in patients with chronic kidney disease not on dialysis, darbepoetin alfa (DA), which has a shorter half-life but is more inexpensive than continuous erythropoietin receptor activator (CERA), is preferred in Korea. This study evaluated the efficacy, safety, and cost-effectiveness of once-in-4-weeks DA compared with once-in-4-weeks CERA in patients with chronic kidney disease not on dialysis.
METHODS
In this randomized, prospective, non-inferiority study, 40 erythropoiesis-stimulating agent-naïve patients with chronic kidney disease not on dialysis were randomized 1:1 to the DA group and CERA group. They received the study drug once in 4 weeks during 10- or 12-week correction period and 24-week efficacy evaluation period. The primary outcomes were the mean difference in the changes in hemoglobin levels between baseline and efficacy evaluation period and hemoglobin response rates during the correction period. The secondary outcomes included differences in adverse events and costs.
RESULTS
DA was non-inferior to CERA for anemia correction; the mean difference in the change in hemoglobin levels between the groups was -0.070 g/dL (95% confidence interval, -0.730 to 0.590 g/dL). Hemoglobin response rates were 100% with DA and 94.1% with CERA. Adverse events were comparable. The mean cost of DA was approximately one-third that of CERA (34,100 ± 7,600 Korean won/4 weeks vs. 115,500 ± 23,600 Korean won/4 weeks; p < 0.001).
CONCLUSION
Once-in-4-weeks DA safely corrects anemia in erythropoiesis-stimulating agent-naïve patients with chronic kidney disease not on dialysis and is more cost-effective than once-in-4-weeks CERA.
PubMed: 38268126
DOI: 10.23876/j.krcp.23.074 -
Journal of the American Society of... Jul 2021Standard care for treating anemia in patients with CKD includes use of erythropoiesis-stimulating agents, which sometimes involves increased risks of cardiovascular...
BACKGROUND
Standard care for treating anemia in patients with CKD includes use of erythropoiesis-stimulating agents, which sometimes involves increased risks of cardiovascular morbidity and mortality. Previous studies in patients with anemia and nondialysis-dependent CKD (NDD-CKD) found significantly elevated hemoglobin levels with use of vadadustat, an oral hypoxia-inducible factor prolyl hydroxylase inhibitor, compared with placebo.
METHODS
In this phase 3, open-label, active-controlled noninferiority trial, we randomized 304 Japanese adults with anemia in NDD-CKD (including erythropoiesis-stimulating agent users and nonusers) to oral vadadustat or subcutaneous darbepoetin alfa for 52 weeks. The primary efficacy end point was average hemoglobin at weeks 20 and 24. Safety data included adverse events (AEs) and serious AEs.
RESULTS
A total of 151 participants received vadadustat and 153 received darbepoetin alfa. Least squares mean of the average hemoglobin at weeks 20 and 24 was 11.66 (95% confidence interval [95% CI], 11.49 to 11.84) g/dl for vadadustat and 11.93 (95% CI, 11.76 to 12.10) g/dl for darbepoetin alfa. The 95% CIs for both treatments were within the target hemoglobin range (11.0-13.0 g/dl), and the lower 95% confidence limit for the difference between groups (-0.50 g/dl) was above the predefined noninferiority margin (-0.75 g/dl), demonstrating noninferiority of vadadustat to darbepoetin alfa. Similar proportions of patients in each group reported AEs and serious AEs. The most frequent AEs with vadadustat were nasopharyngitis, diarrhea, and constipation.
CONCLUSIONS
In Japanese patients with NDD-CKD, vadadustat was noninferior to darbepoetin alfa, was effective up to week 52 in terms of average hemoglobin, and was generally well tolerated. These results suggest that vadadustat may be a potential treatment for anemia in this patient population.
PubMed: 33883252
DOI: 10.1681/ASN.2020091311