Debra Scarlata

A retrospective study of percutaneous endoscopic gastrostomy in ALS patients during the BDNF and CNTF trials

Percutaneous endoscopic gastrostomy (PEG) provides a reliable route for nutrition and hydration in ALS patients with dysphagia. We performed a retrospective analysis of the CNTF and BDNF databases to determine the clinical status of ALS patients within 30 days preceding PEG insertion. This analysis revealed an approximately 50% reduction of function across multiple measures of ALS disease status. A trend to earlier intervention with PEG was apparent upon review of published studies and the CNTF and BDNF studies. By comparing the rate of decline pre- and post-PEG, nutritional supplementation via PEG stabilized the weight loss experienced by patients. Death within 30 days post-PEG was associated with a marked reduction in forced vital capacity (FVC) and identified a group of ALS patients in whom PEG should be cautiously performed. These data emphasize the importance of sequential measurement of FVC in managing ALS patients to guide the timing of nutritional intervention with PEG.

Darbepoetin alfa administered every other week maintains hemoglobin levels over 52 weeks in patients with chronic kidney disease converting from once-weekly recombinant human erythropoietin: results from simplify the treatment of anemia with Aranesp (STAAR).

Background/Aim: Darbepoetin alfa, an effective treatment for anemia of chronic kidney disease (CKD), can be administered at extended intervals. Simplify the Treatment of Anemia with Aranesp® (STAAR), a multicenter, 52-week study, was conducted to assess the efficacy of darbepoetin alfa administered subcutaneously every other week (Q2W) in maintaining hemoglobin (Hb) in CKD patients not receiving dialysis. Methods: This is a subgroup analysis of subjects converted from once-weekly (QW) recombinant human erythropoietin (rHuEPO; US Aranesp package insert) and who received up to 52 weeks of darbepoetin alfa therapy (evaluation period 20–32 weeks). Enrolled subjects had a creatinine clearance ≤70 ml/min or an estimated glomerular filtration rate ≤60 ml/min and transferrin saturation ≧20%. Darbepoetin alfa doses were titrated to maintain Hb levels ≤12 g/dl. The primary endpoint was mean Hb during evaluation. Results: There were 524 subjects enrolled in the study who were previously receiving rHuEPO QW. Mean Hb ± standard deviation was 11.2 ± 1.27 g/dl at baseline, and the least squares mean ± SE was 11.4 ± 0.04 during evaluation. The mean ± SD Q2W darbepoetin alfa dose was 49.7 ± 21.9 µg at baseline and 48.9 ± 35.5 µg at evaluation. Darbepoetin alfa was well tolerated. Conclusions: Study subjects with CKD receiving QW rHuEPO were effectively converted to Q2W darbepoetin alfa, which was well tolerated. Hb levels were maintained over 52 weeks without a significant change in darbepoetin alfa dose.

Baseline characteristics of patients in the Reduction of Events with Darbepoetin alfa in Heart Failure trial (RED-HF)

This report describes the baseline characteristics of patients in the Reduction of Events with Darbepoetin alfa in Heart Failure trial (RED‐HF) which is testing the hypothesis that anaemia correction with darbepoetin alfa will reduce the composite endpoint of death from any cause or hospital admission for worsening heart failure, and improve other outcomes.

Darbepoetin alfa administration to achieve and maintain target hemoglobin levels for 1 year in patients with chronic kidney disease.

OBJECTIVE To assess the efficacy and safety of every-other-week darbepoetin alfa therapy in treating anemia and maintaining hemoglobin levels for 1 year in patients with chronic kidney disease (CKD) who were not undergoing dialysis and who had not previously received erythropolesis-stimulating proteins (ESPs). PATIENTS AND METHODS This multicenter 52-week study (evaluation period, weeks 20-32), a subanalysis of the Simplify the Treatment of Anemia with Aranesp study, enrolled patients with CKD who were not receiving dialysis (creatinine clearance < or =70 mL/min or estimated glomerular filtration rate [GFR] < or =60 mL/min). Patients evaluated in this analysis were not receiving ESPs, had hemoglobin concentrations less than 11 g/dL, and had transferrin saturation of 20% or higher during screening. Patients Initiated every-other-week darbepoetin alfa therapy at 0.75 microg/kg, with the dose subsequently titrated to maintain hemoglobin levels not to exceed 12 g/dL. The first study participant was enrolled on February 4, 2002, and the last participant completed the study on March 31, 2004. RESULTS The analysis included 911 patients (mean [SD] age, 66.4 [14.2] years; 54.3% female; 55.3% white). The least squares mean evaluation hemoglobin concentration was 11.54 g/dL (95% confidence interval, 11.47-11.61 g/dL), and the change from baseline was 1.6 g/dL (95% confidence interval, 1.5-1.7 g/dL). The mean (SD) every-other-week darbepoetin alfa dose during evaluation was 44.5 (33.7) microg. Iron supplementation was administered to 573 patients (62.9%) during the study. Darbepoetin alfa was well tolerated throughout the study period. CONCLUSION Darbepoetin alfa initiated every other week safely and effectively treated anemia and maintained hemoglobin for 1 year in patients with CKD who were not undergoing dialysis and who were not receiving prior ESP therapy.

The association of darbepoetin alfa with hemoglobin and health-related quality of life in patients with chronic kidney disease not receiving dialysis

ABSTRACT Objective: Anemia of chronic kidney disease (CKD) decreases patients’ health-related quality of life (HRQoL). The objective of this subanalysis was to determine the effect of every-other-week (Q2W) darbepoetin alfa on hemoglobin (Hb) levels and HRQoL measures in subjects with CKD who are naïve to erythropoiesis-stimulating agents (ESAs). Methods: STAAR was a 52-week, multicenter, single-arm study. Subject inclusion criteria included: ≥ 18 years of age and creatinine clearance ≤ 70 mL/min or estimated glomerular filtration rate ≤ 60 mL/min/1.73 m2 but not receiving dialysis. Subjects included in this subanalysis were previously naïve to ESAs, had Hb < 11 g/dL, were initiated on subcutaneous Q2W darbepoetin alfa to achieve a Hb level not to exceed 12 g/dL, and had responses to at least one question on the KDQOL-CRI forms administered at baseline, week 12, and week 52. Results: Of 911 ESA-naïve subjects enrolled in the study, 277 (30.4%) were included in this subanalysis. The majority of subanalysis subjects were Caucasian (63.2%) and/or women (54.5%). Mean Hb concentrations and all KDQOL-CRI scores improved significantly between baseline and week 12 ( p < 0.0001), and were maintained until week 52. Darbepoetin alfa was well tolerated. Conclusions: Darbepoetin alfa initiated Q2W achieved and maintained Hb targets, and significantly improved and maintained HRQoL in study subjects with CKD. Limitations of the study must be considered when extrapolating these results to assess the benefits of treatment on HRQoL in the general CKD population.

Preference for monthly darbepoetin alfa dosing in patients with chronic kidney disease not receiving dialysis.

ABSTRACT Objective: To determine patient preference for once-weekly Epoetin alfa versus once-monthly (QM) darbepoetin alfa in patients with chronic kidney disease (CKD) not receiving dialysis. Methods: AMPS (Aranesp † Monthly Preference Study) consisted of two studies of similar design, each with a 2-week screening/baseline period, a 20-week QM darbepoetin alfa dosing period, and an 8-week follow-up period. Patients aged ≥18 years had a nephrologist-reported diagnosis of CKD but were not receiving dialysis, and were required to have at least two hemoglobin levels within 10–12 g/dL and to have been receiving a stable dose (< 25% change) of once-weekly or once- every-other-weekly Epoetin alfa for at least 8 weeks. At week 21, patients could continue on QM darbepoetin alfa or revert back to their previous Epoetin alfa regimen. The primary analysis assessed patient preference at week 21 for QM darbepoetin alfa versus previous onceweekly Epoetin alfa. † Aranesp is a registered trademark of Amgen Inc., Thousand Oaks, California, USA Results: AMPS enrolled 442 patients: 54% were female, 67% were Caucasian, and mean (SD) age was 68.3 (13.5) years. At week 21, 346 patients remained on study. Of the patients converted from once-weekly Epoetin alfa, 86% (138/161) preferred darbepoetin alfa QM, and of all patients who expressed a preference, regardless of previous Epoetin alfa dosing frequency, 96% (305/319) preferred QM darbepoetin alfa. Mean (SD) hemoglobin at week 29 of the study was similar to mean hemoglobin at baseline (for those who completed the study and were receiving QM darbepoetin alfa at week 29: 11.2 [1.1] g/dL at week 29 versus 11.4 [0.7] g/dL at baseline). QM darbepoetin alfa was well tolerated. Conclusion: These data show that the majority of study patients preferred QM darbepoetin alfa to more frequent Epoetin alfa, and that QM darbepoetin alfa maintained hemoglobin levels at week 29 and was well tolerated over the study period. The single-item questionnaire could be a potential limitation of this study and further investigation with a multi-question instrument may be helpful in confirming these results.

A US multicenter, retrospective, observational study of erythropoiesis-stimulating agent utilization in anemic, critically ill patients admitted to the intensive care unit

BACKGROUND Anemia is a common comorbid condition among patients admitted to the intensive care unit (ICU). Darbepoietin alfa and epoetin alfa are erythropoiesis-stimulating agents (ESAs) used to manage anemia in the ICU, although neither drug has an indication in critically ill patients. OBJECTIVE This study describes ESA practice patterns in anemic, critically ill patients admitted to the ICU. METHODS A total of 19 hospitals participated in this US multicenter, retrospective, observational study of adult patients not receiving chronic hemodialysis who were admitted to the ICU for >or=24 hours between February 2005 and September 2005 and who received >or=1 dose of darbepoietin alfa or epoetin alfa. Data on ESA doses, dosing frequencies, hemoglobin levels, and red blood cell (RBC) transfusions were abstracted from electronic medical records. RESULTS A total of 438 patients were included in the analysis, of whom 201 (46%) were treated with darbepoietin alfa and 237 (54%) were treated with epoetin alfa. In the respective groups, similar proportions were male (121/201 [60%] and 126/237 [53%]) and white (146/195 [75%] and 140/184 [76%]); age was also similar (mean [SD], 62 [19] and 60 [18] years). The mean (SD) dose during the first week of ICU stay was 96.5 (40.5) microg with darbepoietin alfa and 33,439 (23,508) U with epoetin alfa. The most commonly prescribed dosing frequency with darbepoietin alfa was once weekly (88.1% of all prescribed doses), with a mean (SD) number of injections of 1.8 (1.75). With epoetin alfa, the most common dosing frequencies were 3 times weekly (35.9%), 1-time dosing (28.5%), and once weekly (24.0%), with a mean (SD) number of injections of 2.9 (4.2). In both groups, the duration of therapy was <or=1 week in ~50% of patients, and the mean change in hemoglobin concentration was 0.8 g/dL. Overall, 47% (darbepoietin alfa) and 44% (epoetin alfa) of patients were RBC transfusion independent (ie, did not require a transfusion during their ICU or hospital stay) after receiving the first ESA dose. CONCLUSION Based on these results, it is apparent that the practice patterns associated with ESA treatment of critically ill patients admitted to the ICU between February 2005 and September 2005 were highly variable.

Treatment of anemia with darbepoetin alfa in heart failure.

Anemia is common in heart failure (HF) patients. A prespecified pooled analysis of 2 randomized, double-blind, placebo-controlled studies evaluated darbepoetin alfa (DA) in 475 anemic patients with HF (hemoglobin [Hb], 9.0-12.5 g/dL). DA was administered subcutaneously every 2 weeks and titrated to achieve and maintain a target Hb level of 14.0+/-1.0 g/dL. By week 27, mean (SD) Hb concentrations did not increase with placebo but increased with DA from 11.5 (0.7) to 13.3 (1.3) g/dL. Hazard ratios (HRs) for DA compared with placebo for all-cause death or first HF hospitalization (composite end point), all-cause death, and HF hospitalization by month 12 were 0.67 (95% confidence interval [CI], 0.44-1.03; P=.067), 0.76 (95% CI, 0.39-1.48; P=.419), and 0.66 (95% CI, 0.40-1.07; P=.093), respectively. Incidence of adverse events was similar in both groups. In post hoc analyses, improvement in the composite end point was significantly associated with the mean Hb change from baseline (adjusted HR, 0.40; P=.017) with DA treatment. There was no increased risk of all-cause mortality or first HF hospitalization with DA in patients with reduced renal function or elevated baseline B-type natriuretic peptide, a biomarker of worse HF. These results suggest that DA is well tolerated, corrects HF-associated anemia, and may have favorable effects on clinical outcomes.

Every-other-week darbepoetin alfa in the correction and maintenance of haemoglobin levels in elderly patients with chronic kidney disease: Post Hoc subanalysis of data from two clinical trials

BackgroundAnaemia is a common complication of chronic kidney disease (CKD) and is associated with increased rates of mortality and diminished quality of life in patients with CKD. Although extended dosing with darbepoetin alfa, an erythropoiesis-stimulating agent (ESA), has been shown to be effective in maintaining haemoglobin (Hb) levels in CKD patients, little information is published on the use of darbepoetin alfa in the correction and maintenance of Hb levels in elderly CKD patients naive to ESA therapy.ObjectiveThis post hoc subanalysis of data from two clinical trials was conducted to investigate the efficacy and safety profile of de novo every-other-week (q2w) darbepoetin alfa in elderly patients with CKD-associated anaemia (not on dialysis), as compared with that of a younger (aged <65 years) patient cohort.MethodsThis analysis was based on data obtained from two open-label, single-arm, multicentre studies of similar design. Patients were aged ≥18 years and naive to previous ESA therapy. Darbepoetin alfa administration was initiated at 0.75 µg/kg and titrated according to individual patient requirements to achieve and maintain Hb levels between 11.0 and 13.0g/dL. The proportion of patients who achieved the primary endpoint, Hb ≥11.0g/dL (study 1), and an Hb level between 11.0 and 13.0 g/dL (study 2) at weeks 4, 8 and 12 weeks and at the end of the study were determined. The results of this subanalysis were stratified by age (<65, 65–74 and ≥75 years).ResultsA total of 203 patients were enrolled in the two studies; 60% were female, 84 (41%) were aged <65 years, 57 (28%) were aged 65–74 years and 62 (31%) were aged ≥75 years. The proportion of patients who achieved Hb levels of ≥11.0 g/dL in study 1 and 11.0–13.0 g/dL in study 2 at week 20 were 93%, 96% and 92%, respectively, for the three age groups. Weight-adjusted q2w darbepoetin alfa doses were similar between the age groups and stable throughout the study period. The mean (standard deviation) Hb levels at week 21 were 12.0 (1.2), 12.7 (1.1) and 12.6 (1.0) g/dL in subjects aged <65, 65–74 and ≥75 years, respectively. The median (standard error) time to reach the primary endpoint was 5.0 (4.7), 5.0 (5.7) and 5.0 (5.7) weeks for subjects aged <65 years, 65–74 years and ≥75 years, respectively. The safety profiles of q2w darbepoetin alfa in both the older and younger age-groups were consistent with those expected for patients with CKD not receiving dialysis.ConclusionsThe results of this study suggest that ESA-naive subjects aged <65, 65–74 and ≥75 years of age with CKD (not receiving dialysis) who received q2w darbepoetin alfa were able to achieve and maintain Hb levels at 11.0–13.0 g/dL. The de novo q2w treatment regimen with darbepoetin alfa described in the present report may help optimize anaemia management in CKD-associated anaemia patients, including those in the older adult population.