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Hematology (Amsterdam, Netherlands) Dec 2023Autoimmune hemolytic anemia (AIHA) can be life-threatening, if hemoglobin (Hb) levels continue to decline after established treatments with glucocorticoids, rituximab,...
Autoimmune hemolytic anemia (AIHA) can be life-threatening, if hemoglobin (Hb) levels continue to decline after established treatments with glucocorticoids, rituximab, intravenous immunoglobulins, and plasmapheresis. Impaired regulatory T cells (Treg) are proposed to alleviate AIHA development through decreased binding of CTLA-4 to antigen-presenting cells. Abatacept is a fusion protein with a CTLA-4 domain and is approved for use in rheumatoid arthritis. It mimics the immunosuppressive CTLA-4 effect of Treg. Thus, application of abatacept in refractory AIHA might be reasonable. A 54-year-old woman with known AIHA was admitted to our clinic due to therapy-refractory hemoglobin decrease to 4.0 g/dl. Previously, multiple courses of glucocorticoids, rituximab, azathioprine, mycophenolate mofetil, cyclophosphamide, bortezomib, and a splenectomy failed to stop or stabilize hemoglobin levels and hemolysis. A new immunosuppressive therapy with cyclosporine was initiated and erythropoiesis was stimulated with darbepoetin alfa. Again, therapy failed even though we tried to support immunosuppressive therapy by reducing the amount of pathogenic antibody through plasmapheresis. We stopped the treatment with cyclosporine and applied abatacept instead. After seven days hemoglobin stabilized at 4.3 g/dl and no further red blood cells transfusions were necessary. About one month later hemolysis aggravated again and azathioprine was added to the ongoing abatacept treatment. Finally, the combination of abatacept and azathioprine led to a long-lasting increase of the Hb level above 11 g/dl six months later. Abatacept can be applied to overcome therapy refractory autoimmune hemolytic anemia but should be combined with an additional immunosuppressive medication such as azathioprine.
Topics: Female; Humans; Middle Aged; Anemia, Hemolytic, Autoimmune; Rituximab; Abatacept; CTLA-4 Antigen; Azathioprine; Hemolysis; Salvage Therapy; Glucocorticoids; Cyclosporins; Hemoglobins
PubMed: 37133319
DOI: 10.1080/16078454.2023.2208010 -
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 -
Biotechnology Journal Aug 2021Great efforts are directed towards improving productivity, consistency and quality of biopharmaceutical processes and products. One particular area is the development of...
Great efforts are directed towards improving productivity, consistency and quality of biopharmaceutical processes and products. One particular area is the development of new sensors for continuous monitoring of critical bioprocess parameters by using online or in-line monitoring systems. Recently, we developed a glucose biosensor applicable in single-use, in-line and long-term glucose monitoring in mammalian cell bioreactors. Now, we integrated this sensor in an automated glucose monitoring and feeding system capable of maintaining stable glucose levels, even at very low concentrations. We compared this fed-batch feedback system at both low (< 1 mM) and high (40 mM) glucose levels with traditional batch culture methods, focusing on glycosylation and glycation of the recombinant protein darbepoetin alfa (DPO) produced by a CHO cell line. We evaluated cell growth, metabolite and product concentration under different glucose feeding strategies and show that continuous feeding, even at low glucose levels, has no harmful effects on DPO quantity and quality. We conclude that our system is capable of tight glucose level control throughout extended bioprocesses and has the potential to improve performance where constant maintenance of glucose levels is critical.
Topics: Animals; Batch Cell Culture Techniques; Bioreactors; Blood Glucose; Blood Glucose Self-Monitoring; CHO Cells; Cricetinae; Cricetulus; Darbepoetin alfa; Glucose
PubMed: 34008350
DOI: 10.1002/biot.202100088 -
Journal of Oncology Pharmacy Practice :... Jun 2021Atezolizumab is currently the only immunotherapy used in conjunction with nab-paclitaxel for locally advanced or triple negative breast cancer. Limited data is available...
INTRODUCTION
Atezolizumab is currently the only immunotherapy used in conjunction with nab-paclitaxel for locally advanced or triple negative breast cancer. Limited data is available regarding hemolytic anemia as a side effect of atezolizumab.
CASE REPORT
We describe a 59-year-old female with a history of triple negative breast cancer with bone metastases presenting for follow up on Cycle 1, Day 15 of atezolizumab and nab-paclitaxel (100 mg/m). Patient's complete blood count (CBC) showed macrocytic anemia, with further workup significant for autoimmune hemolytic anemia (AIHA) attributed to atezolizumab. Patient was started on a high dose prednisone taper starting at 80 mg daily for 16 days, folic acid 1 mg three times daily, iron sucrose, and darbepoetin alfa. Patient's counts recovered, and she was able to start Cycle 2 and continued through Cycle 10 without any additional pre-medications.
DISCUSSION
Hemolytic anemia induced by atezolizumab is a rare side effect that was successfully treated in this patient with a prednisone taper.
Topics: Anemia, Hemolytic, Autoimmune; Antibodies, Monoclonal, Humanized; Antineoplastic Combined Chemotherapy Protocols; Female; Humans; Middle Aged; Prednisone; Triple Negative Breast Neoplasms
PubMed: 32951522
DOI: 10.1177/1078155220957720 -
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 -
Drug Safety Mar 2021Risk evaluation and mitigation strategy (REMS) programs are intended to improve safe use of US Food and Drug Administration-approved drugs. However, controversy exists...
INTRODUCTION
Risk evaluation and mitigation strategy (REMS) programs are intended to improve safe use of US Food and Drug Administration-approved drugs. However, controversy exists over whether they consistently accomplish this goal.
OBJECTIVE
We aimed to assess how initiation of the erythropoiesis stimulating agents (ESAs) darbepoetin alfa and epoetin alfa changed following implementation and enforcement (following a 1-year post-implementation grace period) of a prominent REMS program warning physicians against use in cancer patients with hemoglobin above 10 g/dL.
METHODS
Using claims data from a large US commercial insurance company, we conducted interrupted time-series analyses of darbepoetin alfa and epoetin alfa initiation among adult cancer patients in the 12 months before REMS program implementation, after REMS program implementation, and after REMS program enforcement. We also evaluated differences in inappropriate initiation (hemoglobin tests all above 10 g/dL in the prior month) between the periods.
RESULTS
In total, we identified 3456 darbepoetin alfa initiators and 2632 epoetin alfa initiators. Over the study period, the monthly number of initiators per 100,000 patients with cancer fell from 119 to 32 for darbepoetin alfa and from 82 to 34 for epoetin alfa. However, non-significant post-REMS program implementation level and slope changes per 100,000 adult patients with cancer were observed for darbepoetin alfa (level 0.03 [95% confidence interval (CI) -14.98 to 15.05]; slope 1.94 [95% CI -0.22 to 4.10]) and epoetin alfa (level -4.10 [95% CI -16.85 to 8.65]; slope -0.52 [95% CI -2.35 to 1.32]). Non-significant post-REMS program enforcement level and slope changes were also seen for both drugs (darbepoetin alfa level 1.58 [95% CI -0.58 to 3.74, slope -0.28 [95% CI -15.29 to 14.73]; epoetin alfa level 1.58 (95% CI -0.26 to 3.42], slope 5.74 [95% CI -7.01 to 18.49]). Finally, non-significant changes in inappropriate darbepoetin alfa (60% vs. 53% vs. 57%, p = 0.68) and epoetin alfa (53% vs. 53% vs. 46%, p = 0.41) initiation were observed between the three study periods.
CONCLUSION
REMS program implementation and enforcement were not associated with significant changes in ESA initiation, adding to concerns over the degree to which certain REMS programs enhance patient safety.
Topics: Adult; Anemia; Darbepoetin alfa; Epoetin Alfa; Erythropoietin; Hematinics; Hemoglobins; Humans; Neoplasms; Recombinant Proteins; Risk Evaluation and Mitigation
PubMed: 33206339
DOI: 10.1007/s40264-020-01017-z