A randomized study of extended dosing regimens for initiation of epoetin alfa treatment for anemia of chronic kidney disease.

BACKGROUND AND OBJECTIVES: Although epoetin alfa is commonly initiated weekly (QW) in anemic chronic kidney disease (CKD) patients, recent evidence indicates that it can be initiated every 2 wk (Q2W) and used in maintenance therapy every 4 wk (Q4W). This study examined the feasibility of initiating epoetin alfa Q4W in anemic CKD patients not receiving dialysis. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: This open-label study randomized subjects (1:2:2:2) to treatment with epoetin alfa 10,000 IU QW, 20,000 IU Q2W, 20,000 IU Q4W, or 40,000 IU Q4W for 16 wk. Subjects were > or =18 yr, had hemoglobin <11 g/dl, a glomerular filtration rate of 15 to 90 ml/min per 1.73 m(2), and had not received erythropoietic therapy within 8 wk. The primary analysis was a noninferiority comparison of the 40,000 IU Q4W to the 20,000 IU Q2W group in the per-protocol population with respect to hemoglobin change from baseline to the end of study. RESULTS: Of 262 subjects randomized, 229 comprised the per-protocol population. Mean hemoglobin change from baseline for the 40,000 IU Q4W group (1.24 g/dl) was not inferior to the 20,000 IU Q2W group (1.11 g/dl) with the lower limit of 95% CI, -0.21 g/dl. In the QW, 20,000 IU Q2W, 20,000 IU Q4W, and 40,000 IU Q4W groups, 90%, 87%, 75%, and 86% of subjects, respectively, achieved a hemoglobin increase > or =1 g/dl. Serious adverse events were similar across all groups. CONCLUSIONS: Epoetin alfa can be initiated Q4W in anemic CKD subjects.

Extended epoetin alfa dosing in chronic kidney disease patients: a retrospective review.

BACKGROUND: The effectiveness of extended dosing of epoetin alfa beyond once-weekly (QW) has not been well explored in patients being treated for anaemia of chronic kidney disease (CKD). The current study was undertaken to assess the effectiveness of extended dosing in maintaining haemoglobin (Hb) levels in this population. METHODS: A retrospective chart review was conducted to assess the efficacy of extended epoetin alfa dosing in patients being treated for CKD-related anaemia. Eligible patients were to have received epoetin alfa once every 2 weeks (Q2W), 3 weeks (Q3W), 4 weeks (Q4W), or >Q4W administered subcutaneously for at least 3 months to maintain Hb > or = 11.0 g/dl. Patients were > or =18 years with serum creatinine 1.5 to 6.0 mg/dl for females and 2.0 to 6.0 mg/dl for males, and were not receiving renal replacement therapy. Epoetin alfa dose and dosing frequency were adjusted during treatment at the clinician's discretion. For analysis, patients were stratified into dosing groups based on their most dominant dosing regimen. RESULTS: 243 patients (mean age, 71.5 years; 79% white, 54% female) who received extended epoetin alfa dosing for a mean of 10.3 months were eligible for analysis. Mean baseline estimated glomerular filtration rate and mean serum creatinine were 21.2 ml/min/1.73 m(2) and 3.1 mg/dl, respectively. Primary causes of CKD included hypertension (36%) and diabetes (28%). Most patients (82%) receiving an extended epoetin alfa regimen maintained Hb > or =11.0 g/dl. The most common dosing regimen was Q2W (51%). Mean Hb for each dosing group was maintained between 11.6 g/dl and 12.4 g/dl during the study, and glomerular filtration rate remained stable. Epoetin alfa was well tolerated across all groups. CONCLUSIONS: Data from private community nephrology practices showed that extended epoetin alfa dosing effectively maintained Hb > or =11.0 g/dl in 82% of these selected patients being treated for anaemia of CKD.

Epoetin alfa improves quality of life in anemic HCV-infected patients receiving combination therapy.

Anemia and decreased health-related quality of life (HRQL) are common in patients receiving combination therapy of interferon alfa (IFN) and ribavirin (RBV) for chronic hepatitis C virus (HCV) infection. In a randomized, prospective study evaluating the effectiveness of epoetin alfa in maintaining RBV dose, alleviating anemia, and improving HRQL in anemic (Hb < or = 12 g/dL) HCV-infected patients receiving combination therapy, patients receiving epoetin alfa had significant improvements in HRQL compared with placebo. In this study, 185 patients were randomized to 40,000 units of epoetin alfa subcutaneously weekly or placebo for an 8-week double-blind phase (DBP), followed by an 8-week open-label phase during which all patients received epoetin alfa. To further assess the impact of epoetin alfa on HRQL, post hoc analyses were conducted in the same patient population to compare the HRQL of these patients at randomization with norms of other populations, and to determine the critical relationship between hemoglobin (Hb) levels and HRQL. Mean HRQL scores of anemic HCV-infected patients receiving combination therapy at randomization were significantly lower than those of both the general population and patients who had other chronic conditions. Patients receiving epoetin alfa who had the greatest Hb increases from randomization to the end of the DBP also had the largest improvements in HRQL. Hb improvement was an independent predictor of HRQL improvement in these patients. In conclusion, epoetin alfa provided clinically significant HRQL improvement in HCV-infected patients receiving IFN/RBV therapy.

The prevalence of anemia in patients with chronic kidney disease.

OBJECTIVE: Anemia is a complication of chronic kidney disease and may contribute to adverse clinical outcomes. Early identification and treatment of anemia may improve cardiovascular morbidity and mortality. No large-scale population data are available specifically for patients with chronic kidney disease regarding prevalence of anemia, subpopulations at risk, and relationships between anemia and kidney function. This study was undertaken to address these questions in patients with chronic kidney disease, and investigate the relationship between anemia and glomerular filtration rate. RESEARCH DESIGN AND METHODS: Large-scale, cross-sectional, US multicenter survey; 5222 patients (mean age, 68.2 years; 46.6% male); 237 physician practices. Eligible patients: > or = 18 years of age; serum creatinine: 1.5 mg/dL-6.0 mg/dL (females), 2.0 mg/dL-6.0 mg/dL (males). MAIN OUTCOME MEASURES: Primary study end point: prevalence and severity of anemia (hemoglobin < or = 12 g/dL). Data further stratified by hemoglobin (< or = 12 g/dL, < or = 10 g/dL). RESULTS: Primary etiologies of chronic kidney disease (5222 evaluable patients): diabetes (49.5%); hypertension (33.0%). Glomerular filtration rate: < 60 mL/min/1.73 m2 for 97.7% of evaluable patients. Mean +/- SD serum creatinine level: 2.2 mg/dL +/- 0.9 mg/dL; 2.5 mg/dL +/- 1.0 mg/dL for males, 2.0 mg/dL +/- 0.8 mg/dL for females. Mean +/- SD hemoglobin: 12.2 g/dL +/- 1.6 g/dL (47.7% had hemoglobin < or = 12 g/dL; 8.9% had hemoglobin < or = 10 g/dL). Prevalence of anemia was strongly associated with declining glomerular filtration rate. Percentage of patients with hemoglobin < or = 12 g/dL increased from 26.7% to 75.5% when glomerular filtration rate decreased from > or = 60 mL/min/1.73 m2 to < 15 mL/min/1.73 m2. Prevalence of hemoglobin < or = 10 g/dL increased substantially from 5.2% to 27.2% when glomerular filtration rate diminished from > or = 60 mL/min/1.73 m2 to < 15 mL/min/1.73 m2. After controlling for other patient characteristics associated with increased prevalence of anemia, the prevalence odds ratio for hemoglobin < or = 10 g/dL was 0.54 (0.49-0.60) and for hemoglobin < or = 12 g/dL was 0.68 (0.65-0.72), with each 10-mL/min/1.73 m2 increase in glomerular filtration rate. Predictors of anemia: diabetes, female sex, and race/ethnicity. CONCLUSIONS: Anemia was present in 47.7% of 5222 predialysis patients with chronic kidney disease. Prevalence of anemia increased as kidney function decreased. Certain subgroups are at increased risk for anemia.

Epoetin alfa maintains ribavirin dose in HCV-infected patients: a prospective, double-blind, randomized controlled study.

BACKGROUND & AIMS: Combination therapy with interferon alpha (IFN-alpha) and ribavirin (RBV) or pegylated IFN-alpha (PEG-IFN-alpha)/RBV for chronic hepatitis C virus (HCV) infection often causes anemia, prompting RBV dose reduction/discontinuation. This study assessed whether epoetin alfa could maintain RBV dose, improve quality of life (QOL), and increase hemoglobin (Hb) in anemic HCV-infected patients. METHODS: HCV-infected patients (n = 185) on combination therapy who developed anemia (Hb < or = 12 g/dL) were randomized into a U. S. multicenter, placebo-controlled, clinical trial of epoetin alfa, 40,000 U subcutaneously, once weekly vs. matching placebo. The study design used an 8-week, double-blind phase (DBP) followed by an 8-week, open-label phase (OLP), in which placebo patients were crossed over to epoetin alfa. RESULTS: At the end of the DBP, RBV doses were maintained in 88% of patients receiving epoetin alfa vs. 60% of patients receiving placebo (P < 0.001). Mean QOL scores at the end of the DBP improved significantly on all domains of the Linear Analog Scale Assessment (LASA) and on 7 of the 8 domains of the Short Form-36, version 2 (SF-36v2). Mean Hb increased by 2.2 +/- 1.3 g/dL (epoetin alfa) and by 0.1 +/- 1.0 g/dL (placebo) in the DBP (P < 0.001). Similar results were demonstrated in patients who switched from placebo to epoetin alfa in the OLP. Epoetin alfa was well tolerated; the most common adverse effects were headache and nausea. CONCLUSIONS: Epoetin alfa maintained RBV dose and improved QOL and Hb in anemic HCV-infected patients receiving combination therapy.