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Abstract: TH-PO686

Erythropoiesis-Stimulating Agent Hyporesponsiveness and Anemia Management in the ASCEND-D Trial

Session Information

  • Anemia and Iron Metabolism
    November 03, 2022 | Location: Exhibit Hall, Orange County Convention Center‚ West Building
    Abstract Time: 10:00 AM - 12:00 PM

Category: Anemia and Iron Metabolism

  • 200 Anemia and Iron Metabolism

Authors

  • Waikar, Sushrut S., Boston University School of Medicine and Boston Medical Center, Boston, Massachusetts, United States
  • Coyne, Daniel W., Washington University School of Medicine, St. Louis, Missouri, United States
  • McCausland, Finnian R., Brigham and Women’s Hospital and Harvard Medical School, Boston, Massachusetts, United States
  • Johansen, Kirsten L., Hennepin Healthcare, University of Minnesota, Minneapolis, Minnesota, United States
  • Jha, Vivekanand, George Institute for Global Health, New Delhi, India
  • Obrador, Gregorio T., Universidad Panamericana School of Medicine, Mexico City, Mexico
  • Bhatt, Purav Rahulkumar, GSK, Collegeville, Pennsylvania, United States
  • Mallett, Stephen, GSK, Brentford, United Kingdom
  • Meadowcroft, Amy M., GSK, Collegeville, Pennsylvania, United States
  • Singh, Ajay K., Brigham and Women’s Hospital and Harvard Medical School, Boston, Massachusetts, United States
Background

Erythropoiesis-stimulating agent (ESA) hyporesponsiveness is characterized by high dose ESA and greater use of intravenous (IV) iron. Hypoxia-inducible factor prolyl hydroxylase inhibitors (HIF-PHIs) may be beneficial for iron homeostasis/utilization. Data comparing HIF-PHIs vs ESA in hyporesponders are limited.

Methods

ASCEND-D (NCT02879305) was a phase 3 randomized trial of daprodustat (Dapro) vs ESA in dialysis patients (pts; N=2964). ESA hyporesponsiveness was defined as baseline ESA-resistance index >2.0 or epoetin dose >450U/kg/week. Both treatment groups used protocolized dosing of study drug and iron to achieve/maintain hemoglobin (Hb) 10.0–11.0g/dL. A rescue algorithm for anemia management allowed use of IV iron and/or red blood cell (RBC) transfusion, with discontinuation of study drug for persistent Hb <9g/dL or >2units RBC transfusion. Statistical analyses included analysis of covariance with treatment x subgroup interactions.

Results

At baseline, 12% of pts were ESA-hyporesponsive (ESA-HR) (Table). During the trial, higher Dapro and ESA doses were required in the ESA-HR vs non-ESA-HR group. Mean change in Hb from baseline to weeks 28–52 for Dapro vs ESA: ESA-HR group, 0.01g/dL; non-ESA-HR group, 0.21g/dL (p-interaction=0.04). Mean IV iron use was lower with Dapro vs ESA in the ESA-HR group (-31.7mg) but similar in those not ESA-HR (-6.9mg; p-interaction=0.09). A greater number of RBC transfusions and discontinuations due to rescue therapy was seen in Dapro vs ESA in ESA-HR pts; the opposite was observed in non-ESA-HR pts.

Conclusion

Baseline responsiveness to ESA led to different patterns of anemia management for Dapro vs ESA, with evidence of lower IV iron utilization with Dapro in those who were ESA hyporesponsive at baseline.

Figure. Summary of Dapro and ESA hyporesponsiveness and anemia management in the ASCEND-D Trial

Funding

  • Commercial Support