A Randomized Controlled Study Comparing Once-Weekly to Every-2-Week and Every-4-Week Dosing of Epoetin Alfa in CKD Patients with Anemia

Extended-interval dosing of epoetin alfa (EPO) is commonly used to treat anemia in patients with chronic kidney disease (CKD). This study aimed to demonstrate that EPO dosed every 2 weeks (Q2W) and every 4 weeks (Q4W) was noninferior to once-weekly (QW) dosing. 430 anemic subjects with stage 3 to 4 CKD receiving a stable QW dose of EPO were randomized 1:1:2 to QW, Q2W, and Q4W dosing for 36 weeks. Hemoglobin (Hb) was measured weekly, and the dose of EPO was adjusted to maintain an Hb level of 11.0 to 11.9 g/dl. The primary endpoint was change in Hb from baseline to the average of the last 12 weeks of treatment. Both the Q2W and Q4W dosing groups were noninferior to the QW group. The estimated difference of the mean change in Hb between Q2W and QW was -0.03 g/dl; and between Q4W and QW was -0.09 g/dl. From weeks 13 to 37, the mean percentage of weeks per subject with Hb 10.0 to 11.9 g/dl, inclusive, was 81% for QW, 81% for Q2W, and 75% for Q4W. Death occurred, respectively, in 4%, 3%, and 4%; thromboembolic vascular events occurred in 3%, 5%, and 3%; and serious adverse events occurred in 22%, 26%, and 26% of subjects. Q2W and Q4W EPO dosing maintained Hb levels in subjects with stage 3 to 4 CKD. Deaths, thromboembolic vascular events, and serious adverse events were comparable across the dosing groups.