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Overall Adverse Event Profile of Vadadustat versus Darbepoetin Alfa for the Treatment of Anemia Associated with Chronic Kidney Disease in Phase 3 Trials

INTRODUCTION: Anemia frequently occurs in chronic kidney disease (CKD), is associated with poor quality of life and cardiovascular outcomes, and its treatment represents a considerable economic burden to the healthcare system. Although effective, the current standard of care for the treatment of ane...

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Autores principales: Agarwal, Rajiv, Anand, Sanjeev, Eckardt, Kai-Uwe, Luo, Wenli, Parfrey, Patrick S., Sarnak, Mark J., Solinsky, Christine M., Vargo, Dennis L., Winkelmayer, Wolfgang C., Chertow, Glenn M.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: S. Karger AG 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9909618/
https://www.ncbi.nlm.nih.gov/pubmed/36450264
http://dx.doi.org/10.1159/000528443
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author Agarwal, Rajiv
Anand, Sanjeev
Eckardt, Kai-Uwe
Luo, Wenli
Parfrey, Patrick S.
Sarnak, Mark J.
Solinsky, Christine M.
Vargo, Dennis L.
Winkelmayer, Wolfgang C.
Chertow, Glenn M.
author_facet Agarwal, Rajiv
Anand, Sanjeev
Eckardt, Kai-Uwe
Luo, Wenli
Parfrey, Patrick S.
Sarnak, Mark J.
Solinsky, Christine M.
Vargo, Dennis L.
Winkelmayer, Wolfgang C.
Chertow, Glenn M.
author_sort Agarwal, Rajiv
collection PubMed
description INTRODUCTION: Anemia frequently occurs in chronic kidney disease (CKD), is associated with poor quality of life and cardiovascular outcomes, and its treatment represents a considerable economic burden to the healthcare system. Although effective, the current standard of care for the treatment of anemia in chronic kidney disease patients with erythropoiesis-stimulating agents requires chronic/ongoing injections, making the treatment less accessible or desirable to patients not treated by in-center maintenance hemodialysis. Furthermore, safety concerns, including an increased risk of cardiovascular events and mortality, have emerged from their use in studies targeting hemoglobin concentrations in the normal or near-normal range. The orally active hypoxia-inducible factor prolyl hydroxylase inhibitor vadadustat may offer advantages over erythropoiesis-stimulating agents by correcting anemia via pathways activating endogenous erythropoietin production. METHODS: To comprehensively analyze the safety profile of vadadustat in patients with dialysis-dependent and non-dialysis-dependent CKD-related anemia, we pooled the safety populations from each of the four trials in the phase 3 clinical program (n = 7,373) and compared the risk of treatment-emergent adverse events (TEAEs) for each treatment arm. RESULTS: In patients randomized to vadadustat versus darbepoetin alfa, rates of TEAEs (88.9% vs. 89.3%), treatment-emergent serious adverse events (58.0% vs. 59.3%), and TEAEs leading to death (16.1% vs. 16.2%) were similar, as were rates of adverse events of special interest, including cardiovascular-, hepatic-, and neoplasm-related adverse events. DISCUSSION/CONCLUSION: Among patients with CKD-related anemia treated with vadadustat, we observed similar rates of adverse events relative to those treated with darbepoetin alfa.
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spelling pubmed-99096182023-02-10 Overall Adverse Event Profile of Vadadustat versus Darbepoetin Alfa for the Treatment of Anemia Associated with Chronic Kidney Disease in Phase 3 Trials Agarwal, Rajiv Anand, Sanjeev Eckardt, Kai-Uwe Luo, Wenli Parfrey, Patrick S. Sarnak, Mark J. Solinsky, Christine M. Vargo, Dennis L. Winkelmayer, Wolfgang C. Chertow, Glenn M. Am J Nephrol Patient-Oriented, Translational Research: Research Article INTRODUCTION: Anemia frequently occurs in chronic kidney disease (CKD), is associated with poor quality of life and cardiovascular outcomes, and its treatment represents a considerable economic burden to the healthcare system. Although effective, the current standard of care for the treatment of anemia in chronic kidney disease patients with erythropoiesis-stimulating agents requires chronic/ongoing injections, making the treatment less accessible or desirable to patients not treated by in-center maintenance hemodialysis. Furthermore, safety concerns, including an increased risk of cardiovascular events and mortality, have emerged from their use in studies targeting hemoglobin concentrations in the normal or near-normal range. The orally active hypoxia-inducible factor prolyl hydroxylase inhibitor vadadustat may offer advantages over erythropoiesis-stimulating agents by correcting anemia via pathways activating endogenous erythropoietin production. METHODS: To comprehensively analyze the safety profile of vadadustat in patients with dialysis-dependent and non-dialysis-dependent CKD-related anemia, we pooled the safety populations from each of the four trials in the phase 3 clinical program (n = 7,373) and compared the risk of treatment-emergent adverse events (TEAEs) for each treatment arm. RESULTS: In patients randomized to vadadustat versus darbepoetin alfa, rates of TEAEs (88.9% vs. 89.3%), treatment-emergent serious adverse events (58.0% vs. 59.3%), and TEAEs leading to death (16.1% vs. 16.2%) were similar, as were rates of adverse events of special interest, including cardiovascular-, hepatic-, and neoplasm-related adverse events. DISCUSSION/CONCLUSION: Among patients with CKD-related anemia treated with vadadustat, we observed similar rates of adverse events relative to those treated with darbepoetin alfa. S. Karger AG 2023-01 2022-11-30 /pmc/articles/PMC9909618/ /pubmed/36450264 http://dx.doi.org/10.1159/000528443 Text en Copyright © 2022 by The Author(s). Published by S. Karger AG, Basel https://creativecommons.org/licenses/by-nc/4.0/This article is licensed under the Creative Commons Attribution-NonCommercial 4.0 International License (CC BY-NC). Usage and distribution for commercial purposes requires written permission.
spellingShingle Patient-Oriented, Translational Research: Research Article
Agarwal, Rajiv
Anand, Sanjeev
Eckardt, Kai-Uwe
Luo, Wenli
Parfrey, Patrick S.
Sarnak, Mark J.
Solinsky, Christine M.
Vargo, Dennis L.
Winkelmayer, Wolfgang C.
Chertow, Glenn M.
Overall Adverse Event Profile of Vadadustat versus Darbepoetin Alfa for the Treatment of Anemia Associated with Chronic Kidney Disease in Phase 3 Trials
title Overall Adverse Event Profile of Vadadustat versus Darbepoetin Alfa for the Treatment of Anemia Associated with Chronic Kidney Disease in Phase 3 Trials
title_full Overall Adverse Event Profile of Vadadustat versus Darbepoetin Alfa for the Treatment of Anemia Associated with Chronic Kidney Disease in Phase 3 Trials
title_fullStr Overall Adverse Event Profile of Vadadustat versus Darbepoetin Alfa for the Treatment of Anemia Associated with Chronic Kidney Disease in Phase 3 Trials
title_full_unstemmed Overall Adverse Event Profile of Vadadustat versus Darbepoetin Alfa for the Treatment of Anemia Associated with Chronic Kidney Disease in Phase 3 Trials
title_short Overall Adverse Event Profile of Vadadustat versus Darbepoetin Alfa for the Treatment of Anemia Associated with Chronic Kidney Disease in Phase 3 Trials
title_sort overall adverse event profile of vadadustat versus darbepoetin alfa for the treatment of anemia associated with chronic kidney disease in phase 3 trials
topic Patient-Oriented, Translational Research: Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9909618/
https://www.ncbi.nlm.nih.gov/pubmed/36450264
http://dx.doi.org/10.1159/000528443
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