Hemoglobin Variability with Extended Dosing of Epoetin Alfa in Patients with Chronic Kidney Disease and Not on Dialysis

OBJECTIVES Hemoglobin (Hgb) variability when treating anemia in pre‐dialysis chronic kidney disease (CKD) patients with erythropoietin stimulating agents (ESAs) may be an important safety consideration, as significant Hgb fluctuations over time appear to be associated with worse outcomes, especially cardiovascular‐related outcomes. We analyzed Hgb variability in subjects receiving epoetin alfa (EPO) with extended dosing regimens. METHODS We conducted a post‐hoc analysis to evaluate Hgb variability in 2 trials of EPO in CKD anemia; both examined Hgb response during dosing intervals up to 4 weeks. Study 1 examined 4 EPO maintenance regimens of every 1 to 4 weeks for 16 weeks. Study 2 examined EPO initiation and maintenance dosing of every 2 weeks for 28 weeks. RESULTS During the maintenance periods evaluated, Hgb variability (mean within‐subject standard deviations) was 0.75 (0.32), 0.66 (0.29), 0.65 (0.30), and 0.74 (0.36) g/dL, with 10KQW, 20KQ2W, 30KQ3W, and 40KQ4W regimens in study 1 (10,000 IU [10K] once weekly [QW], 20,000 IU [20K] every 2 weeks [Q2W], 30,000 IU [30K] every 3 weeks [Q3W], or 40,000 IU [40K] every 4 weeks [Q4W]), and was 0.59 (0.27) g/dL with 20KQ2W in study 2. Serious thrombovascular events were seen in 4 patients in study 1 and in 3 patients in study 2. CONCLUSIONS Our analysis of CKD patients treated with extended dosing of EPO revealed no relationships between Hgb variability and administered dose or dose interval, comparable with published results of other ESAs.