Intravenous Epoetin Alfa-epbx versus Epoetin Alfa for Treatment of Anemia in End-Stage Kidney Disease - PubMed (original) (raw)

Randomized Controlled Trial

. 2018 Aug 7;13(8):1204-1214.

doi: 10.2215/CJN.11631017. Epub 2018 Jun 19.

Affiliations

Randomized Controlled Trial

Intravenous Epoetin Alfa-epbx versus Epoetin Alfa for Treatment of Anemia in End-Stage Kidney Disease

Steven Fishbane et al. Clin J Am Soc Nephrol. 2018.

Abstract

Background and objectives: This study was conducted to compare the safety and efficacy of intravenous epoetin alfa-epbx, an epoetin alfa biosimilar, to epoetin alfa in patients on hemodialysis with ESKD and anemia.

Design, setting, participants, & measurements: In this 24-week, multicenter, double-blind comparative efficacy and safety study, 612 patients on hemodialysis with ESKD and anemia who had stable hemoglobin and were receiving stable doses of intravenous epoetin alfa were randomized (1:1) to intravenous epoetin alfa or epoetin alfa-epbx. Dosing was adjusted according to the epoetin alfa prescribing information. The coprimary efficacy end points were the least squares mean difference between the two treatments in mean weekly hemoglobin level and mean weekly epoetin dose per kilogram of body weight during the last 4 weeks of treatment.

Results: The least squares mean difference between epoetin alfa-epbx and epoetin alfa in weekly hemoglobin was -0.12 g/dl and the 95% confidence interval (-0.25 to 0.01) was contained within the prespecified equivalence margin (-0.5 to 0.5 g/dl). The least squares mean difference between epoetin alfa-epbx and epoetin alfa in weekly epoetin dose per kilogram of body weight was 0.37 U/kg per week, and the 95% confidence interval (-10.40 to 11.13) was contained within the prespecified equivalence margin (-45 to 45 U/kg per week). Incidences of adverse events (77.1% versus 75.3%), serious adverse events (24.9% versus 27.0%), and deaths (_n_=5 versus 6) were similar between the epoetin alfa-epbx and epoetin alfa groups, respectively. Five patients tested positive for anti-recombinant human erythropoietin antibodies at baseline, and two additional patients (_n_=1 per group) developed anti-recombinant human erythropoietin antibodies while on study treatment. All patients tested negative for neutralizing antibodies, and no patient in either group experienced an event of pure red cell aplasia.

Conclusions: This 24-week, comparative, clinical trial in patients on hemodialysis with ESKD and anemia demonstrated there is no clinically meaningful difference in efficacy or safety between epoetin alfa-epbx and epoetin alfa.

Keywords: Antibodies, Neutralizing; Biosimilar Pharmaceuticals; Body Weight; Confidence Intervals; Double-Blind Method; EPO protein, human; Epoetin Alfa; Hemoglobins; Incidence; Kidney Failure, Chronic; Least-Squares Analysis; Red-Cell Aplasia, Pure; anemia; chronic kidney disease; erythropoietin; renal dialysis.

Copyright © 2018 by the American Society of Nephrology.

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Figures

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Graphical abstract

Figure 1.

Figure 1.

This comparative clinical trial of IV epoetin alfa-epbx versus epoetin alfa was a randomized, active-controlled, parallel-group, double-blind study including a screening period, 24-week double-blind treatment period, follow-up visit, and 48-week, open-label long-term safety study with epoetin alfa-epbx. aPatients who discontinued early from epoetin alfa-epbx or epoetin alfa received a nonstudy drug standard-of-care ESA until either the follow-up visit or entry into the open-label, long-term safety study. bPatients who completed the treatment period and who did not enter the open-label, long-term safety study underwent a follow-up visit at week 28, 4 weeks after the end of week 24 study activity assessments. cPatients had up to 28 days from completion of the week 24 visit to enter into the open-label, long-term safety study and be treated with IV epoetin alfa-epbx for an additional ≤48 weeks. dCoprimary efficacy end points were assessed during the last 4 weeks of the treatment period.

Figure 2.

Figure 2.

This flow diagram shows patient disposition through each phase of the comparative clinical trial of IV epoetin alfa-epbx versus epoetin alfa.

Figure 3.

Figure 3.

Mean (SD) weekly hemoglobin level (g/dl) and mean (SD) weekly epoetin dose by body weight (U/kg per week) were similar between epoetin alfa-epbx and epoetin alfa over the duration of the treatment period. ITT population. There was no statistical difference in mean weekly hemoglobin levels (_P_=0.76) or mean weekly epoetin dose per kilogram of body weight (_P_=0.11) between the two treatment groups over 24 weeks.

Figure 4.

Figure 4.

Mean and median systolic and diastolic BPs after dialysis were unchanged over time and similar between epoetin alfa-epbx and epoetin alfa. The box represents the 25th and 75th percentiles and the tails represent the minimum and maximum observed values; the median is indicated by the horizontal line, and the mean by *.

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