Management Of Anemia In Patients Research Articles

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.

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. 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. 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). 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.

Correlation between ultrafiltration rate and hemoglobin level and erythropoietin response in hemodialysis patients

This study aimed to investigate the correlation between ultrafiltration rate (UFR) and hemoglobin levels and erythropoietin (EPO) response in patients receiving maintenance hemodialysis (MHD). 225 MHD patients were divided into three groups according to the UFR: < 10 ml/h/kg, 10–13 ml/h/kg, and >13 ml/h/kg. Clinical parameters and prognosis were compared among the groups. Multiple linear correlation and regression analyses were conducted. SPSS 26.0 (IBM, Chicago, IL, USA) was used to analyze all statistics. The UFR < 10 ml/h/kg group was older than the other groups (p < 0.05). The UFR > 13 ml/h/kg group had the highest SpKt/V (p < 0.05), monthly EPO dose/weight (p < 0.001), and EPO resistance index (p < 0.001), as well as the lowest dry weight (p < 0.001), BMI (p < 0.001), hemoglobin (p < 0.001), hematocrit (p < 0.05), and red blood cell count (p < 0.05). Multiple linear regression analysis showed that sex, dry weight, UFR, calcium, phosphorus, albumin, and C-reactive protein levels were associated with hemoglobin levels. Multivariate logistic regression analysis revealed that a higher UFR was associated with lower hemoglobin levels, while male sex and higher levels of calcium and albumin were associated with higher hemoglobin levels. High UFR is associated with more severe anemia and EPO resistance in MHD. This study provides new insights into anemia management in patients undergoing hemodialysis.

Development of a Practical Nomogram for Personalized Anemia Management in Patients Treated with Ataxia Telangiectasia and Rad3-related Inhibitor Camonsertib.

Camonsertib is a highly selective and potent inhibitor of ataxia telangiectasia and Rad3-related (ATR) kinase. Dose-dependent anemia is a class-related on-target adverse event often requiring dose modifications. Individual patient risk factors for the development of significant anemia complicate the selection of a "one-size-fits-all" ATR inhibitor (ATRi) dose and schedule, possibly leading to suboptimal therapeutic doses in patients at low risk of anemia. We evaluated whether early predictors of anemia could be identified to ultimately inform a personalized dose-modification approach. On the basis of preclinical observations and a mechanistic understanding of ATRi-related anemia, we identified several potential factors to explore in a multivariable linear regression modeling tool for predicting hemoglobin level ahead of day 22 (cycle 2) of treatment. In patients treated with camonsertib monotherapy (NCT04497116), we observed that hemoglobin decline is consistently preceded by reticulocytopenia, and dose- and exposure-dependent decreases in monocytes. We developed a nomogram incorporating baseline and day 8 hemoglobin and reticulocyte values that predicted the day 22 hemoglobin values of patients with clinically valuable concordance (within 7.5% of observations) 80% of the time in a cross-validation performance test of data from 60 patients. The prediction of future hemoglobin decrease, after a week of treatment, may enable a personalized, early dose modification to prevent development of clinically significant anemia and resulting unscheduled dose holds or transfusions.

Luspatercept for the Treatment of Anemia in Non-Transfusion-Dependent β-Thalassemia: Final Safety and Efficacy Data from the BEYOND Trial

Background: Suboptimal anemia management in patients (pts) with non-transfusion-dependent (NTD) β-thalassemia may lead to serious clinical complications. Improvements in hemoglobin (Hb) levels were shown to significantly decrease the risk of developing morbidities (Musallam KM, et al. Ann Hematol 2022;101:203-204; Musallam KM, et al. Ann Hematol 2021;100:1903-1905). There is a need for therapies that increase Hb levels besides red blood cell transfusions (RBCT), which lead to secondary iron overload. Primary and longer-term data from the BEYOND study showed that luspatercept led to significant increases in Hb levels and had a manageable safety profile in pts with NTD β-thalassemia (Taher AT, et al. Lancet Haematol 2022;9:e733-e744; Taher AT, et al. Blood 2022;140[suppl 1];8210-8212). Here we report the final data (up to last patient last visit [LPLV] date Nov 28, 2022), of the phase 2, randomized, double-blind, placebo-controlled BEYOND trial (NCT03342404). Methods: Eligible pts (N = 145) had NTD (defined as receiving ≤ 5 RBC units in the 24 wk before randomization) β-thalassemia or HbE/β-thalassemia, Hb levels ≤ 10 g/dL. Pts were randomized to luspatercept (N = 96; 1.0-1.25 mg/kg) or placebo (N = 49) subcutaneously Q3W for ≥ 48 wk. Pts continued to receive best supportive care when required. Pts who crossed over from placebo to luspatercept were not included in this analysis. Mean Hb increase ≥ 1.0 g/dL (any 12-/24-wk interval) and ≥ 1.5 g/dL from baseline (any 12-wk interval), duration of mean Hb increase ≥ 1.0 g/dL and ≥ 1.5 g/dL from baseline, iron parameters, RBCT, and safety were evaluated up to the LPLV date. Results: As of Nov 28, 2022, 93/134 (69.4%) pts on luspatercept transitioned to the long-term follow-up study (NCT04064060): 66/96 (68.8%) pts in the luspatercept arm and 27/38 (71.1%) pts who crossed over from placebo to luspatercept after study unblinding. A total of 76/96 (79.2%) pts in the luspatercept arm completed 144 wk of treatment (tx), with 55/96 (57.3%) completing 192 wk of tx; 28/96 (29.2%) pts on luspatercept discontinued tx. The median (range) luspatercept tx duration was 202.8 (15.0-242.3) wk (Table) and 61.1 (3.0-138.0) wk with placebo. Pts had a durable increase in Hb ≥ 1.0 g/dL from baseline (by 12-wk interval) through wk 240 of luspatercept tx (Figure). In the luspatercept arm, 91/96 (94.8%) pts had a mean Hb increase ≥ 1.0 g/dL from baseline during any 12-wk interval (Table). The mean (standard deviation [SD]) total duration of mean Hb increase ≥ 1.0 g/dL from baseline (any 12-wk interval) with luspatercept was 1136.0 (491.9) days. The proportion of pts achieving a mean Hb increase ≥ 1.5 g/dL during any 12-wk interval over the entire tx period was 80/96 (83.3%) and 4/49 (8.2%) in the luspatercept and placebo arms, respectively. At baseline, 83/96 and 42/49 pts in the luspatercept and placebo arms, respectively, were RBCT-free. The proportion of pts who remained RBCT-free was 78.1% (75/96) and 57.1% (28/49) in the luspatercept and placebo arms, respectively. For pts who received RBCT, the mean time to first RBCT was 482.0 days with luspatercept and 202.6 days with placebo. The mean change from baseline in serum ferritin (SF) level at wk 96 was +76.45 µg/L with luspatercept (n = 90) and +211.51 µg/L with placebo (n = 35). The mean change from baseline in SF level stabilized with longer luspatercept tx (wk 192: 49.14 µg/L [n = 71]; wk 240: 52.19 µg/L [n = 51]). The mean change from baseline in liver iron content in the luspatercept arm was −1.23 mg/g dry weight (dw) at wk 96 (n = 8) and −0.79 mg/g dw at wk 144 (n = 54). The 10 most frequently reported adverse events (AEs; ≥ 5% of pts) with luspatercept were headache, back pain, bone pain, COVID-19, arthralgia, pyrexia, pain in extremity, fatigue, diarrhea, and hypertension. Rates of serious and grade 3-4 AEs in the luspatercept arm were 24.0% [23/96] and 34.4% [33/96]), respectively. In the luspatercept arm, thromboembolic events were reported in 2/96 pts, extramedullary hemopoietic masses in 10/96 pts (all grade 1-2), and there were no malignancies. Few AEs led to tx discontinuation in the luspatercept arm (5/96 [5.2%]); no new safety signals were identified. Summary: The final results from the BEYOND study show that pts with NTD β-thalassemia treated with luspatercept maintained clinically meaningful and durable erythroid responses. The safety profile of luspatercept was manageable, and extended luspatercept exposure did not raise new safety concerns.

Anemia Treatment, Hemoglobin Variability, and Clinical Events in Patients With Nondialysis-Dependent CKD in Japan.

Anemia management in patients with non-dialysis-dependent chronic kidney disease has attracted attention with the introduction of novel therapeutic agents; however, few studies have provided comprehensive epidemiologic information. A retrospective cohort study was conducted in adult patients with stage ≥3a non-dialysis-dependent chronic kidney disease and hemoglobin <11 g/dL (January 2013-November 2021; N=26,626) to assess longitudinal treatment patterns, hemoglobin, and iron parameters (ferritin and transferrin saturation) for anemia management. Time-dependent Cox proportional hazard models were applied to assess the risk of clinical events, including death, cardiovascular events, dialysis introduction, and red-blood-cell transfusion, associated with temporal fluctuation patterns of hemoglobin levels. The cumulative incidence of anemia treatment initiation within 12 months was 37.1%, including erythropoiesis-stimulating agents 26.5%, iron oral 16.8%, iron intravenous 5.1%, and hypoxia-inducible factor prolyl hydroxylase inhibitor 0.2%. The mean (±standard deviation) hemoglobin levels were improved from 9.9±1.2 g/dL to 10.9±1.6 g/dL at 12 months. Despite erythropoiesis-stimulating agents or hypoxia-inducible factor prolyl hydroxylase inhibitor therapy, 30.1% of patients remained hemoglobin <10 g/dL. The risks of premature death, cardiovascular events, dialysis introduction, and red-blood-cell transfusion were significantly higher in groups with consistently low hemoglobin or low-amplitude hemoglobin fluctuation around the lower limit of target hemoglobin range than in patients with target hemoglobin range (p <0.05). Likewise, significantly higher risks for dialysis introduction and red-blood-cell transfusion were associated with high-amplitude hemoglobin fluctuation across target hemoglobin range were observed. The findings underscore the importance of stable hemoglobin control within the target range to reduce the mortality and morbidity risks in patients with non-dialysis-dependent chronic kidney disease while highlighting the suboptimal and heterogeneous treatment of anemia in clinical practice.

A multicenter descriptive analysis of anemia management in hemodialysis patients and its association with quality of life

BackgroundAppropriate management of anemia in patients with hemodialysis (HD) involves the administration of iron supplementation and erythropoietin-stimulating agents (ESAs), in addition to monitoring the response. This study aimed to evaluate the treatment of anemia in patients with HD and describe the factors associated with it and its effect on health-related quality of life (HRQOL).MethodsThe study was cross-sectional in design. The patients were included from three dialysis centers in Palestine from June to September 2018. The data collection instrument consisted of two portions; the initial portion contained demographic and clinical information on the patients, while the second consisted of the European Quality of Life 5-Dimension Scale (EQ-5D-5 L) and the visual analog scale EQ (EQ-VAS).ResultsThe study included 226 patients. Their mean age (± SD) was 57 ± 13.9 years. The mean level of hemoglobin (Hb) (± SD) was 10.63 ± 1.71 g/dl, and 34.1% of the patients had a Hb level of 10-11.5 g/dl. All patients who required iron supplementation received it intravenously with a dose of 100 mg of iron sucrose. Almost 86.7% of the patients received darbepoetin alfa intravenously at 0.45 mcg/kg a week, and 24% had a Hb level > 11.5 g/dl. There were significant associations between the level of Hb and the number of comorbid diseases and the ESA that was received. However, other demographics and clinical factors did not significantly affect Hb levels. Certain variables, such as exercise, were a predictor of a higher quality of life. It should be noted that there is a significant impact of a low Hb value on the EQ-VAS scale.ConclusionsOur study found that more than half of the patients had a Hb level below the recommended goal of Kidney Disease Improving Global Outcomes (KDIGO). Furthermore, a significant association was found between patients’ Hb level and HRQOL. Therefore, the appropriate treatment of anemia in patients with HD should be followed by adherence to the guideline recommendations, which consequently improves the HRQOL of HD patients, in addition to obtaining optimal therapy.

Complications of red cell exchange for anemia management in patients with transfusion-dependent thalassemia.

In the Rare Blood Disorders clinic at the University of Alberta in Edmonton, red cell exchange (RCE) was utilized in transfusion-dependent thalassemia (TDT) patients with severe iron overload despite oral chelation and no access to iron infusion pumps for parenteral chelation. It was hypothesized that RCE would be less iron loading compared to simple transfusion. The purpose of this study is to document observations of the potential risks and benefits of RCE in TDT patients. TDT patients treated with RCE were identified and consented for enrolment according to local research ethics standards. Seven patients were enrolled in the study. Charts were retrospectively reviewed from the time of initiation of RCE to the time of the most recent RCE or clinic follow-up. Outcomes were documented and analyzed by descriptive analysis. The average age was 30 years. 85.7% were male. 100% were on oral chelation therapy and had hyperferritinemia at baseline. Outcomes included hepatic iron overload (5 of 7), cardiac dysfunction (3 of 7), worsening splenomegaly or extramedullary hematopoiesis (5 of 7), syncopal events during RCE (2 of 7), and new antibodies (1 of 7). Iron overload improved after escalated oral chelation, not in relation to RCE initiation. We hypothesize complications were higher than expected due to inadequate hematocrit increment and lack of suppression of ineffective erythropoiesis. With no observed benefit in iron status, and high complication rates, we did not find evidence to recommend RCE in patients with TDT. This case series is a hypothesis-generating study on transfusion techniques in TDT.

#4927 DARBEPOETIN ALFA ONCE IN 4 WEEKS CORRECTS ANEMIA IN PATIENTS WITH CHRONIC KIDNEY DISEASE NOT ON DIALYSIS

Abstract Background and Aims In anemia management in patients with CKD not on dialysis (CKD ND), darbepoetin alfa (DA), which has shorter half-life but lower cost than continuous erythropoietin receptor activator (C.E.R.A.), is preferred in actual clinical practice in Korea. The current study evaluated the efficacy and safety of DA every 4 weeks (Q4W) compared to C.E.R.A. Q4W administration for in erythropoiesis-stimulating agent (ESA)-naïve patients with CKD ND. Method In this randomized, prospective, noninferiority study, 40 ESA-naïve patients with CKD ND were randomized 1:1 to receive either DA or C.E.R.A. Q4W during a 12-week correction period and 24-week efficacy evaluation period (EEP). Two primary efficacy end points were analysed: 1) the mean difference in the changes in haemoglobin (Hb) levels between baseline and EEP and 2) the Hb response rates defined as the proportion of patients who reached the target Hb level range (10-11 g/dL) during correction period. The non-inferiority margin is pre-defined as: 1) The lower limit of the 95% confidence interval (CI) is &amp;gt;-0.75 g/dL for the mean difference in the changes in Hb levels and 2) &amp;gt;60% for Hb response rates. Safety profiles including changes in blood pressure (BP), laboratory safety parameters, and frequency of all adverse events (AEs) were monitored and analysed during study period. Results The mean difference in the changes in Hb levels between the two groups was [0.375 g/dL; 95% confidence interval (CI), -0.446 to 1.196)] and [-0.070 g/dL; 95% CI, -0.730 to -0.590] in the intent-to-treat (ITT) and per-protocol (PP) population, respectively (Fig. 1). The Hb response rates in correction period were comparable between DA and C.E.R.A. group; [100%; 95% CI, 81.4 to 100] versus [94.1%; 95% CI, 71.3 to 99.8)] and [100%; 95% CI, 79.4 to 100] versus [100%; 95% CI: 88.2 to 100)] in ITT and PP population, respectively (Fig. 2). The mean estimated glomerular filtration rate, systolic and diastolic BP, sodium, and potassium level over time were not different during total study period between two groups (P = 0.264, 0.999, 0.823, 0.941, and 0.978). All of the AEs in each group were reported to be mild to moderate in intensity. Peripheral edema, neck pain, herpes zoster, and dyspnea occurred in DA group (20%) and urinary tract infection, dyspnea, and femur neck fracture occurred in C.E.R.A. group (15%). There were no serious AEs which led to discontinuation of the treatment. All AEs were mild to moderate in severity, and they are probably not associated with the study drugs and were successfully cured. The reasons for discontinuation of the drugs were starting HD or follow-up loss, but not due to the administered study drugs. No subjects received RBC transfusion or iron replacement therapy in both groups. There was no death during the study period. Conclusion These study results suggest that DA Q4W has non-inferiority in anemia correction efficacy and similar safety profiles compared to C.E.R.A. Q4W in ESA-naïve patients with CKD ND.

Step-Wise Management of Anemia in Patients With Chronic Kidney Disease in Primary Care: Qualitative Study.

Anemia is common in chronic kidney disease (CKD) and is associated with increased cardiovascular risk and reduced quality of life, but is often sub-optimally managed. Most patients are managed in primary care alongside other comorbidities. Interventions to improve the management of anemia in CKD in this setting are needed. We conducted a qualitative study to evaluate how an audit-based education (ABE) intervention might improve the management of anemia in CKD. We explored outcomes that would be relevant to practitioners and patients, that exposed variation of practice from National Institute for Health and Care Excellence (NICE) guidelines, and whether the intervention was feasible and acceptable. Practitioners (n = 5 groups) and patients (n = 7) from 4 London general practices participated in discussions. Practitioners welcomed the evidence-based step-wise intervention. However, prescribing erythropoiesis-stimulating agents (ESAs) was felt to be outside of their scope of practice. There was a gap between NICE guidance and clinical practice in primary care. Iron studies were not well understood and anemia management was often conservative or delayed. Patients were often unaware of having CKD, and were more concerned about their other comorbidities, but largely trusted their GPs to manage them appropriately. The first steps of the intervention were welcomed by practitioners, but they expressed concerns about independently prescribing ESAs. Renal physicians and GPs could develop shared care protocols for ESA use in primary care. There is scope to improve awareness of renal anemia, and enhance knowledge of guideline recommendations; and our intervention should be modified accordingly.

Effect of hyperparathyroidism on anemia management in patients with hemodialysis dependent end stage renal disease

Effect of hyperparathyroidism on anemia management in patients with hemodialysis dependent end stage renal disease

Hemoglobin and Clinical Outcomes in Hemodialysis: An Analysis of US Medicare Data From 2018 to 2020

Anemia management in patients treated with maintenance dialysis remains a challenge. We sought to update information in this area by evaluating the association between hemoglobin and various outcome and utilization measures using data-rich Medicare sources. Observational cohort study using data from the Consolidated Renal Operations in a Web-enabled Network and Medicare claims. We studied 371,250 prevalent patients treated with hemodialysis, covering 3,326,072 patient-months in2019. Monthly patient hemoglobin concentrations. We examined several outcomes, including mortality, all-cause hospitalization, cause-specific hospitalization, and emergency department utilization in the month following the exposure measurement. For each monthly observation period, we calculated unadjusted and adjusted (for demographics and comorbid condition) hazard ratios using Cox regression. The hemoglobin concentration was<10.5g/dL for 40% of observations. We found an inverse association between mortality and hemoglobin measured over a range from<9g/dL (HR, 2.53; 95% CI, 2.45-2.61; P<0.0001, reference=10.5-11g/dL) to 11-11.5g/dL (HR, 0.92; 95% CI, 0.89-0.96; P<0.0001). Mortality riskstarted to increase at hemoglobin levels>11.5g/dL. All-cause hospitalization, cause-specific hospitalization (including cardiovascular, infection, and several subcategories including coronavirus disease 2019 hospitalization), and emergency department utilization were inversely associated with hemoglobin concentration, with risk reduction stabilizing at hemoglobin levels of approximately 11.5-12g/dL and higher. As with prior observational studies, the observed associations are not necessarily causal. In a large US hemodialysis population, there were better clinical outcomes at higher hemoglobin concentrations over short exposure and follow-up periods, consistent with other observational studies that generally used longer exposure and follow-up times. Mortality risk increased at hemoglobin concentrations>11.5g/dL, consistent with findings from erythropoiesis-stimulating agent clinical trials. The apparently beneficial short-term effects associated with higher hemoglobin concentrations suggest that hemoglobin measurements capture unmeasured elements of patient risk.

Treatment Patterns and Outcomes in Lower-Risk, Non-Del(5q) Myelodysplastic Syndromes: Findings from a Global Real-World Medical Record Review Study

Background: Myelodysplastic syndromes (MDS) are a group of clonal hematopoietic stem cell malignancies defined by ineffective hematopoiesis and peripheral blood cytopenias. Patients often present with anemia and frequently require red blood cell transfusions (RBCTs), which may lead them to become transfusion-dependent (TD). This results in poor quality of life and reduced survival. In patients with non-del(5q) lower-risk (LR)-MDS, the standard of care includes erythropoiesis-stimulating agents (ESAs) ± granulocyte colony-stimulating factor as first-line (1L) therapy; however, although clinical trials have demonstrated efficacy, there is little evidence from real-world settings. This study aimed to assess real-world data to investigate treatment patterns and prevailing hematologic outcomes in patients with non-del(5q) LR-MDS. Methods: In this retrospective medical record review, eligible patients ≥ 18 years of age diagnosed with non-del(5q) LR-MDS between July 1, 2013 and September 30, 2018 were identified by participating hematologist-oncologists in the US, Canada (CAN), UK, and EU (France, Germany, Spain). Demographics, clinical characteristics, treatment patterns, and hematologic outcomes data were abstracted (June-November 2021) and reported descriptively. Aggregated analyses were performed using pooled US/CAN and UK/EU data sets for the overall cohort and for patient subgroups treated with clinician-defined 1L and second-line (2L) ESA-containing regimens. Results: Medical record data were abstracted for 119 patients with non-del(5q) LR-MDS in US/CAN (median age, 61.5 years; 71.4% male) and 245 patients in UK/EU (median age, 67.3 years; 71.4% male). Median follow-up duration from MDS diagnosis was 50.5 months (US/CAN) and 67.8 months (UK/EU). At initial diagnosis, 50.4% (US/CAN) and 53.5% (UK/EU) of patients had Low-risk MDS (per Revised International Prognostic Scoring System). Of the 71 patients in US/CAN and 123 patients in UK/EU who were tested successfully for the SF3B1 mutation, 16.9% (US/CAN) and 15.5% (UK/EU) were positive. Most of the patients initiated 1L therapy (US/CAN: 109 [91.6%]; UK/EU: 225 [91.8%]) and more than one-third initiated a 2L therapy (US/CAN: 45 [37.8%]; UK/EU: 89 [36.3%]). In 1L, 2.8% patients in US/CAN and 2.2% in UK/EU received treatment with lenalidomide. Most patients were treated with ESA-containing regimens in 1L, with a median duration of therapy of ≥ 2 years (US/CAN: 97 [89.0%], of which 86.6% was ESA monotherapy; UK/EU: 203 [90.2%], of which 85.7% was ESA monotherapy). Treatment characteristics and hematologic outcomes for patients treated with ESAs are presented in the Table. Among patients who were TD before 1L ESA treatment (36 [37.1%] US/CAN; 104 [51.2%] UK/EU), a small proportion (2.8% US/CAN; 14.4% UK/EU) became transfusion independent (TI) during 1L; RBCT reduction threshold (≥ 50%) was met by 41.7% in US/CAN (median duration, 23 months) and 52.9% in UK/EU (median duration, 13 months). Among patients treated with ESA-containing regimens in 2L (12 [26.7%] US/CAN; 26 [29.2%] UK/EU), most had been treated with ESA in 1L (US/CAN: 10 [83.3%]; UK/EU: 22 [84.6%]). The most frequently reported reasons for reinitiating treatment with ESAs in 2L were overall health status (54.6% US/CAN; 40.9% UK/EU), treatment efficacy (45.5% US/CAN; 63.6% UK/EU), and disease characteristics (36.4% US/CAN; 45.5% UK/EU). In the subgroup of patients who reinitiated ESA in 2L, the most frequently reported reasons for discontinuation of 1L ESA were patient decision (45.5% US/CAN; 22.7% UK/EU), completion of planned course of therapy (45.5% US/CAN; 18.2% UK/EU), and progressive disease (36.4% US/CAN; 68.2% UK/EU). Conclusions: In this real-world study, the most frequently used treatments for the management of anemia in patients with non-del(5q) LR-MDS were ESA-containing regimens. A considerable proportion of patients were TD before initiating 1L ESA therapy. For those who were re-treated with ESAs in 2L, the most common reasons for treatment reinitiation were health status, disease characteristics, and reported treatment efficacy, although only a small fraction of patients who were TD at 1L ESA initiation became TI. These findings highlight an unmet need in anemia management among patients with non-del(5q) LR-MDS, and a requirement for new and more effective treatment options. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

Prevalence, incidence, and treatment of anaemia in patients with non-dialysis-dependent chronic kidney disease: findings from a retrospective real-world study in Italy

BackgroundLimited data are available on the epidemiology and clinical management of anaemia in patients with non-dialysis-dependent chronic kidney disease (NDD-CKD).MethodsThis retrospective observational study was based on records from databases of five Local Health Units across Italy. Adults with reported NDD-CKD stage 3a–5 between 1 January 2014 and 31 December 2016 were identified. Annual prevalence and incidence of anaemia (age- and sex-standardised) and clinical management (erythropoiesis-stimulating agents [ESAs], intravenous [IV] iron, and blood transfusions) were evaluated. Eligibility for ESAs was defined by ≥ 2 records of Hb < 10 g/dL, or < 11 g/dL over 6 months.ResultsOverall, 101,143 individuals with NDD-CKD (3a–5) recorded between 2014 and 2016 were identified, of whom 40,020 (39.6%) were anaemic. Prevalence of anaemia was 33.8% in 2016 and incidence of anaemia was stable (11.4–12.4%) from 2014 to 2016. Prevalence and incidence of anaemia increased with CKD stage. Among eligible patients, 12.8% with Hb < 11 g/dL and 15.5% with Hb < 10 g/dL received ESAs, and the proportion treated increased with CKD stage. Among ESA-treated patients with at least 2 years of follow up, 18.4% and 19.3% received IV iron in the Hb < 11 and < 10 g/dL groups, respectively, and 16.5% and 19.4% received blood transfusions. Corresponding proportions for the overall anaemic cohort were 9.0% and 11.3%, respectively.ConclusionsAnaemia is a significant issue in patients with NDD-CKD. Low rates of ESA treatment indicate a potential treatment gap and suggest that anaemia may not be adequately controlled in many patients.Graphical abstract

Management of anaemia in French dialysis patients: results from a large epidemiological retrospective study.

Limited real-world data are available in Europe, especially France, regarding the therapeutic management of anaemia in patients with dialysis-dependent chronic kidney disease (DD CKD). This retrospective, longitudinal, observational study was based on medical records from the MEDIAL database of not-for-profit dialysis units in France. From January to December 2016, we included eligible patients (≥18 years), with a diagnosis of CKD and receiving maintenance dialysis. Patients with anaemia were followed up for 2 years after inclusion. Patient demographic data, anaemia status, CKD-related anaemia treatments, and treatment outcomes including laboratory test results were evaluated. Of 1632 DD CKD patients identified from the MEDIAL database, 1286 had anaemia; 98.2% of patients with anaemia were receiving haemodialysis at index date (ID). Of patients with anaemia, 29.9% had haemoglobin (Hb) levels of 10-11g/dL and 36.2% had levels of 11-12g/dL at ID. Furthermore, 21.3% had functional iron deficiency and 11.7% had absolute iron deficiency. The most commonly prescribed treatments at ID for patients with DD CKD-related anaemia were intravenous (IV) iron with erythropoietin-stimulating agents (ESAs) (65.1%). Among patients initiating ESA treatment at ID or during follow-up, 347 (95.3%) reached the Hb target of 10-13g/dL and maintained response within the target Hb range for a median duration of 113 days. Despite combined use of ESAs and IV iron, duration within the Hb target range was short, suggesting that anaemia management can be further improved.

1593P Real-world data on anemia management in patients with solid tumors and malignant lymphoma in Germany

Anemia is a frequent complication in patients with breast cancer (BC), gastrointestinal tumors (GC), lung cancer (LC) and malignant lymphomas (ML). Guidelines (GL) on anemia management (ESMO, DGHO) provide dedicated algorithms for diagnosis and treatment of anemia. GL adherence (GLAD) was analyzed. This was a retrospective sample analysis representative for practices and hospitals in Germany. Data on tumor treatments and anemia management was collected from records of cancer patients (pts) with grade ≥ 2 anemia diagnosed between January and June 2021. Definition of diagnosis GLAD score (GLAD-D): 2 points (pt) for full adherence, 1 pt for a lack in differential diagnosis on iron metabolism. 0 pt if differential diagnosis is missing. Treatment GLAD score (GLAD-T): 2 pt for full adherence to GL recommendation in relation to diagnosis. 1 pt for indicated red blood cells (RBC) as only anemia therapy or no therapy in pts with Hb ≥8g/dl. 0 pt for RBC without indication, p.o. iron substitution under inflammatory conditions (CRP>5mg/l) or vitamin B12 or folate deficiency without substitution. Data from 1046 pts (311 BC, 371 GC, 260 LC, 104 ML) were collected from 143 centers. Hb-values at diagnosis of anemia were 8-10 g/dl in 899 (85.9%) pts, 6-8g/dl in 135 (12.9%) and <6g/dl (1.2%) in 12 pts. 456 pts were treated with RBC (43.6%), 198 (18.9%) with iron substitution, 106 (10.1%) with ESA and 60 (5.7%) with vitamin B12. 60.6% of the pts with iron substitution were treated i.v. and 39.4% p.o. 37.5% of pts with RBC had no indication in the sense of the restrictive RBC policy recommended by the GLs. GLAD was poor in diagnosis and treatment: GLAD-D was 2 pt in 310 pts (29.6%) of pts, 1 pt at 168 (16.1%) and 0 pt in 568 (54.3%) pts. GLAD-T was 2 pt in 270 pts (25.8%), 1 pt in 310 (29.6%) and 0 pt in 466 (44.6%). Higher GLAD-D correlated significantly to a higher GLAD-T (τB 0.262, p<0.001). Full GLAD-T (2 pt) was significantly associated with a greater Hb increase (p<0.001) at 28 days (10.2 vs. 9.7 g/dl) and at 2 months (10.4 vs 9.9 g/dl). GLAD is insufficient in Germany, especially concerning liberal transfusion policy and the lack of differential diagnostics of iron metabolism. Pts with anemia management as per GL had a significantly greater Hb-increase.

Luspatercept in patients with non-transfusion dependent β-thalassaemia

Ineffective erythropoiesis leads to the development of chronic anaemia and iron overload in patients with non-transfusion dependent β-thalassemia, which is associated with significant morbidity, risk of mortality, and loss of health-related quality of life (HRQoL) especially in patients who have haemoglobin concentrations lower than 10 g/dL.1 There are no approved drugs directed at the management of anaemia in patients with non-transfusion dependent β-thalassemia, leaving supportive care with occasional red blood cell transfusions and iron chelation as the only approved therapeutic options for these patients.

Luspatercept for the treatment of anaemia in non-transfusion-dependent β-thalassaemia (BEYOND): a phase 2, randomised, double-blind, multicentre, placebo-controlled trial

In patients with non-transfusion-dependent β-thalassaemia, haemoglobin concentrations lower than 10 g/dL are associated with a higher risk of morbidity, mortality, and impaired quality of life. No drugs are specifically approved for anaemia management in patients with non-transfusion-dependent β-thalassaemia, other than transfusion therapy administered infrequently in accordance with patients' needs. We assessed the efficacy and safety of luspatercept versus placebo in patients with non-transfusion-dependent β-thalassaemia. We did a phase 2, randomised, double-blind, multicentre, placebo-controlled trial in 12 centres in six countries (Thailand [n=1], Lebanon [n=1], Greece [n=2], Italy [n=5], the UK [n=1], and the USA [n=2]). Eligible patients were aged 18 years or older, had confirmed diagnosis of β-thalassaemia or haemoglobin E/β-thalassaemia (concomitant α-globin deletion, mutation, or duplication were allowed), and a baseline haemoglobin concentration of 10·0 g/dL or lower. All patients were non-transfusion-dependent. Patients were randomly assigned (2:1) to luspatercept or placebo using an interactive response technology system and stratified by baseline haemoglobin concentration (≥8·5 g/dL vs <8·5 g/dL) and baseline Non-Transfusion-Dependent β-thalassaemia-Patient-Reported Outcome Tiredness/Weakness domain score (≥3 vs <3). All patients, study site staff, and sponsor representatives (who reviewed the data), except for designated individuals, were masked to drug assignment until the time the study was unblinded. Luspatercept or placebo was given once subcutaneously every 3 weeks for 48 weeks in the double-blind treatment period. Luspatercept was started at 1·0 mg/kg with titration up to 1·25 mg/kg, or reduction in the event of toxicity or excessive haemoglobin concentration increase. The primary endpoint was achievement of an increase from baseline of 1·0 g/dL or higher in mean haemoglobin concentration over a continuous 12-week interval during weeks 13-24, in the absence of transfusions. The primary efficacy and safety analyses were done in the intention-to-treat population. This trial is registered at ClinicalTrials.gov, NCT03342404, and is ongoing. Between Feb 5, 2018, and Oct 14, 2019, 160 patients were screened for eligiblity, of whom 145 were randomly assigned to luspatercept (n=96) or placebo (n=49). 82 (57%) patients were female and 63 (43%) were male. 44 (30%) patients were Asian, 87 (60%) were White, and 14 (10%) identified as another race. The study met its primary endpoint: 74 (77%) of 96 patients in the luspatercept group and none in the placebo group had an increase of at least 1·0 g/dL in haemoglobin concentration (common risk difference 77·1 [95% CI 68·7-85·5]; p<0·0001). The proportion of patients with serious adverse events was lower in the luspatercept group than in the placebo group (11 [12%] vs 12 [25%]). Treatment-emergent adverse events most commonly reported with luspatercept were bone pain (35 [37%]), headache (29 [30%]), and arthralgia (28 [29%]). No thromboembolic events or deaths were reported during the study. Luspatercept represents a potential treatment for adult patients with non-transfusion-dependent β-thalassaemia, for whom effective approved treatment options are scarce. Celgene and Acceleron Pharma.

Management of Perioperative Anemia in Patients that Performed Abdominal Major Surgery.

Introduction: Anemia is a recognized predictor of adverse postoperative outcomes in patients during abdominal major surgery. The management of perioperative anemia involves many strategies. Pre-operative anemia has adverse outcomes in major surgery and is called the fourth factor. Anemia was then classified into mild, moderate, and severe depending on hemoglobin level. It is present almost in 40% of patients that performed elective major surgery. Patients with preoperative anemia are associated with an increased rate of blood transfusion together with a risk for high morbidity and mortality. The most usual cause of preoperative anemia is iron deficiency, which can be treated with oral/intravenous iron depending on the time scheduled for surgery. A review concluded that anemia recovery earlier with preoperative intravenous iron than with oral iron supplement. A perioperative erythropoietin injection is also a reasonable approach for patients with hemoglobin between 10 and 13 g/dL and if autologous blood donation is performed. The protocol requires a baseline complete blood count and iron studies and all patients should receive iron supplementation during erythropoietin therapy. The next strategy is stabilized macro/ microcirculation to optimize the patient´s tolerance to bleeding. Recent recommendation, in general, suggests no bridging therapy consider it only if high thrombotic risk. Finally, targeted surgery should be used to reduce intraoperative and postoperative bleeding. We recommend a restrictive transfusion strategy. Allogeneic blood transfusion is associated with an increased incidence of nosocomial infections. Postoperative anemia must be treated with the use of intravenous iron. We ought to know fresh frozen plasma used in deficit in factor V, XI, in dose 15-30ml/kg and be aware of its complications as immunomodulation, acute lung injury, and cardiac overload.&#x0D; Conclusion: Our goal is to improve patients´ clinical outcomes.

POSB241 A Retrospective Study of the Management of Anaemia in Patients with Dialysis-Dependent Chronic Kidney Disease in France: The Amack Study

Anaemia, a common complication of chronic kidney disease (CKD), is associated with poor outcomes. This study aimed to describe current routine anaemia management in dialysis-dependent (DD) CKD patients in France.

Contemporary outcomes of anemia in US patients with chronic kidney disease.

ABSTRACTBackgroundLong-term clinical outcome data from patients with non-dialysis-dependent (NDD) chronic kidney disease (CKD) are lacking. We characterized patients with NDD-CKD and anemia using real-world data from the USA.MethodsThis retrospective longitudinal observational study evaluated integrated Limited Claims and Electronic Health Record Data (IBM Health, Armonk, NY), including patients ≥18 years with two or more estimated glomerular filtration rate (eGFR) measures <60 mL/min/1.73 m2 ≥90 days apart. Anemia was defined as the first observed hemoglobin <10 g/dL within 6-month pre- and post-CKD index date. Data were analyzed from January 2012 to June 2018. Patients with documented iron-deficiency anemia at baseline were excluded.ResultsComprising 22 720 patients (57.4% female, 63.9% CKD stage 3, median hemoglobin 12.5 g/dL), median (interquartile range) follow-up for patients with and without anemia were 2.9 (1.5–4.4) and 3.8 (2.2–4.8) years, respectively. The most prevalent comorbidities were dyslipidemia (57.6%), type 2 diabetes mellitus (38.8%) and uncontrolled hypertension (20.0%). Overall, 23.3% of patients had anemia, of whom 1.9% and <0.1% received erythropoiesis-stimulating agents (ESAs) or intravenous iron, respectively. Anemia prevalence increased with CKD stage from 18.2% (stage 3a) to 72.8% (stage 5). Patients with anemia had a higher incidence rate of hospitalizations for heart failure (1.6 versus 0.8 per 100 patient-years), CKD stage advancement (43.5 versus 27.5 per 100 patient-years), and a 40% eGFR decrease (18.1 versus 7.3 per 100 patient-years) versus those without anemia.ConclusionsAnemia, frequently observed in NDD-CKD and associated with adverse clinical outcomes, is rarely treated with ESAs and intravenous iron. These data suggest that opportunities exist for improved anemia management in patients with NDD-CKD.