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Abstract: FR-PO0200

Simulated Effect of Continuous Erythropoietin Receptor Activator Monthly vs. Every Two-Week Dosing on Hemoglobin in Anemia Correction of Patients on Dialysis

Session Information

Category: Anemia and Iron Metabolism

  • 200 Anemia and Iron Metabolism

Authors

  • Kovacevic, Tomislav, Vifor Fresenius Medical Care Renal Pharma Ltd, St. Gallen, SG, Switzerland
  • Studer, Milena, F Hoffmann-La Roche AG, Basel, BS, Switzerland
  • Mouksassi, Samer, Certara Inc, Radnor, Pennsylvania, United States
  • Frey, Nicolas, F Hoffmann-La Roche AG, Basel, BS, Switzerland
Background

Methoxy polyethylene glycol epoetin beta (Continuous EPO Receptor Activator C.E.R.A.) is indicated for treatment of anemia in chronic kidney disease. For anemia correction it can be dosed every two weeks (Q2W) or once monthly (QM) in non-dialysis patients, but only Q2W in dialysis patients. Lack of clinical trial data on QM dosing in incident dialysis limits our understanding of differences between QM and Q2W for anemia correction in dialysis. Link between C.E.R.A. pharmacokinetic (PK) and pharmacodynamic (PD) (i.e. hemoglobin (Hb) levels) has been well characterized in a modeling and simulation (M&S) framework.

Methods

Clinical trial simulations using the PK/PD model compared QM (1.2 µg/kg) vs. Q2W (0.6 µg/kg) C.E.R.A. initiation for anemia correction (Hb<10g/dl) in ESA-naïve hemodialysis patients, using US dosing rules and Hb target of 10-11g/dl. Simulations also included lower starting doses: 0.4 and 0.2 µg/kg Q2W and 0.8 and 0.4 µg/kg QM.
Hb levels, dosing patterns, and cumulative C.E.R.A. dose, including the impact of lower per kg starting doses were simulated over 24 weeks (correction) based on data from 326 historical dialysis trial participants.

Results

While Hb target attainment was slightly slower with QM, it enabled more time for appropriate dose titration. During correction period, QM resulted in fewer Hb excursions above 11 or 12 g/dl and less frequent complete dose holds compared to Q2W (Fig 1). Over 6 months cumulative C.E.R.A. dose was higher with QM, but QM individual dose distribution was more even. Label-defined starting doses, versus lower starting doses per kg, caused a more rapid and more significant Hb rise to and above US target for both Q2W and QM.

Conclusion

Modeling and simulation analysis suggest that initiating C.E.R.A. with QM dosing in dialysis patients may provide more optimal anemia correction vs. standard Q2W dosing, with fewer Hb excursions outside the target range and easier dose adjustments. Lower starting doses per kg warrant consideration. Prospective trials or real-world data are needed for confirmation.

Median Hb and CERA dose over time

Funding

  • Commercial Support – Vifor Fresenius Medical Care Renal Pharma

Digital Object Identifier (DOI)