Aim: To determine whether extended epoetin alfa dosing schedules of up to once every four weeks are as effective as weekly dosing in maintaining hemoglobin (Hb) levels in patients with anemia of chronic kidney disease (CKD).
Methods: This randomized, open-label trial enrolled patients with anemia of CKD not on dialysis. Patients were required to have a stable Hb level (> or = 11.0 g/dl) and to have been previously receiving epoetin alfa for two or more months. Patients were randomized to one of four subcutaneously administered epoetin alfa dosing regimens: 10,000 units (U) once weekly (QW), 20,000 U every two weeks (Q2W), 30,000 U every three weeks (Q3W) or 40,000 U every four weeks (Q4W). Dose reductions, but not escalations, were permitted. Patients received treatment for a total of 16 weeks. The primary endpoint for the trial was the mean final Hb measurements of the QW, Q2W, Q3W, and Q4W groups. The primary efficacy analyses were non-inferiority assessments of the mean final Hb measurements of the Q2W, Q3W, and Q4W groups, compared with the QW group. The primary efficacy analyses were performed using a modified intent-to-treat (MITT) population, defined as all patients meeting all inclusion/exclusion criteria (or, if not satisfying all criteria, were granted an exemption at study entry), and who were randomized and received at least one dose of study medication. A per-protocol population, based on all patients who met the MITT criteria and completed the entire study, was used to evaluate the robustness of the MITT results. Quality of life was assessed for all dosing groups throughout the study. Safety was based on all patients randomized who received at least one dose of study medication.
Results: A total of 519 patients were enrolled; 445 were included in the MITT population. The four treatment groups were comparable with respect to baseline characteristics. The primary etiologies of CKD were diabetes (45.7%) and hypertension (29.9%). The mean baseline Hb, serum creatinine and glomerular filtration rate for all patients were 11.9 +/- 0.8 g/dl, 3.1 mg/dl, and 21.1 ml/min/1.73 m2, respectively. The mean baseline transferrin saturation was 25.2% and the mean ferritin was 201.9 ng/ml for all patients. All groups had a mean final Hb of > 11.0 g/dl. The mean final Hb levels of the Q2W and Q4W groups were statistically non-inferior to the QW group. The results of the per-protocol analysis were consistent with the MITT results. In addition, 93.5%, 89.5%, 77.2%, and 76.0% of patients maintained a mean Hb > or = 11.0 g/dl throughout the course of the study in the QW, Q2W, Q3W, and Q4W groups, respectively. Quality of life was maintained or improved from baseline to final within each dosing group. There were no significant differences in the mean final quality of life scores between the QW group and the Q2W, Q3W, and Q4W groups. Among the 513 patients evaluated for safety, epoetin alfa was well tolerated with no differences in adverse events between groups. The incidence of thrombotic adverse events was low (2.5% of patients), as was mortality (1.4% of patients).
Conclusions: Approximately 90% of patients dosed once every two weeks and over 75% of patients dosed once every three or four weeks maintained mean Hb levels > or = 11.0 g/dl, consistent with the Kidney Disease Outcomes Quality Initiative (K/DOQI) guidelines. This study suggests that extended epoetin alfa dosing schedules are effective and safe for maintaining Hb, and may offer the possibility of increased flexibility and convenience for the majority of patients with the anemia of CKD.