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

Abstract

Background and objectives: 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.Design, setting, participants, & measurements: 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.Results: 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.Conclusions: 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.

Dose of Erythropoiesis-Stimulating Agents and Adverse Outcomes in CKD: A Metaregression Analysis

“…In addition, 92 potentially relevant systematic reviews were identified and screened, 10 of which were evaluated in full-text; 172 potentially relevant citations were identified from the references of these systematic reviews, of which 23 satisfied the selection criteria. After removal of duplicate reports, 31 unique trials with 72 study arms (cohorts) were included 8,28–57 . All eligible studies were in English.…”

“…The attrition rates over the full duration of follow-up, reported in 29 trials, ranged from 0% to 80%. Six trials reported drop-out rates of less than 10% 29,31,35,49,56,57 and 7 trials of more than 40% 33,37,38,41,43,46,48 . Two trials did not report their drop-out rates 39,53 .…”

A Dosing Algorithm for Erythropoietin Alpha in Older Adults with Heart Failure and a Preserved Ejection Fraction

“…Accordingly, several studies have demonstrated that equivalent target hemoglobin levels can be maintained at much lower doses of epoetin alfa when administered subcutaneously than intravenously [17,18]. Indeed some have shown that subcutaneous epoetin alfa dosing frequency can be reduced in some patients to once every 2–4 weeks, without compromising efficacy and potentially reducing subject burden and costs [19].…”

“…Accordingly, several studies have demonstrated that equivalent target hemoglobin levels can be maintained at much lower doses of epoetin alfa when administered subcutaneously than intravenously [17,18]. Indeed some have shown that subcutaneous epoetin alfa dosing frequency can be reduced in some patients to once every 2-4 weeks, without compromising efficacy and potentially reducing subject burden and costs [19]. We employed weekly administration of epoetin alfa, as it has been shown to be effective in maintaining hemoglobin concentrations in the majority of stable hemodialysis patients [20], among subjects with chronic kidney disease but not on dialysis [21] and in HIV positive subjects [22].…”

Treating anemia associated with chronic renal failure with erythropoiesis stimulators: Recombinant human erythropoietin might be the best among the available choices

“…Subsequent research demonstrated that equal therapeutic effect (Hb control) could be achieved with much lower individual/total weekly doses (e.g., 3-fold lower), and with less frequent dosing, e.g., twice or once/week (not affecting drug utilization). It has been further demonstrated that subcutaneous (s.c.) administration (particularly convenient for patients not yet on dialysis) allows for further reduction in drug utilization (by 20-30%) with additional flexibility in dosing, showing equivalent therapeutic effect and drug utilization with thrice, twice or once a week dosing (tiw, biw, qw, respectively), or even with once every 2 weeks (q2w) or every 4 weeks (q4w) dosing [5][6][7]. This flexibility allows for individualization of treatment in agreement with the (desired) therapeutic effect, rationalization of drug utilization and also contributes to lower occurrence of adverse effects [5][6][7].…”