Overall Adverse Event Profile of Vadadustat versus Darbepoetin Alfa for the Treatment of Anemia Associated with Chronic Kidney Disease in Phase 3 Trials
© 2022 The Author(s). Published by S. Karger AG, Basel..
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.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2022 |
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| Erschienen: |
2022 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:53 |
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| Enthalten in: |
American journal of nephrology - 53(2022), 10 vom: 29., Seite 701-710 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Agarwal, Rajiv [VerfasserIn] |
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| Links: |
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| Anmerkungen: |
Date Completed 26.01.2023 Date Revised 11.02.2023 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.1159/000528443 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM349629471 |
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| 100 | 1 | |a Agarwal, Rajiv |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Overall Adverse Event Profile of Vadadustat versus Darbepoetin Alfa for the Treatment of Anemia Associated with Chronic Kidney Disease in Phase 3 Trials |
| 264 | 1 | |c 2022 | |
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| 500 | |a Date Completed 26.01.2023 | ||
| 500 | |a Date Revised 11.02.2023 | ||
| 500 | |a published: Print-Electronic | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a © 2022 The Author(s). Published by S. Karger AG, Basel. | ||
| 520 | |a 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 | ||
| 520 | |a 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 | ||
| 520 | |a 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 | ||
| 520 | |a 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 | ||
| 650 | 4 | |a Randomized Controlled Trial | |
| 650 | 4 | |a Clinical Trial, Phase III | |
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Research Support, Non-U.S. Gov't | |
| 650 | 4 | |a Adverse events | |
| 650 | 4 | |a Anemia | |
| 650 | 4 | |a Chronic kidney disease | |
| 650 | 4 | |a Hypoxia-inducible factor pathway | |
| 650 | 4 | |a Vadadustat | |
| 650 | 7 | |a Darbepoetin alfa |2 NLM | |
| 650 | 7 | |a 15UQ94PT4P |2 NLM | |
| 650 | 7 | |a vadadustat |2 NLM | |
| 650 | 7 | |a Erythropoietin |2 NLM | |
| 650 | 7 | |a 11096-26-7 |2 NLM | |
| 650 | 7 | |a Hematinics |2 NLM | |
| 650 | 7 | |a Hemoglobins |2 NLM | |
| 700 | 1 | |a Anand, Sanjeev |e verfasserin |4 aut | |
| 700 | 1 | |a Eckardt, Kai-Uwe |e verfasserin |4 aut | |
| 700 | 1 | |a Luo, Wenli |e verfasserin |4 aut | |
| 700 | 1 | |a Parfrey, Patrick S |e verfasserin |4 aut | |
| 700 | 1 | |a Sarnak, Mark J |e verfasserin |4 aut | |
| 700 | 1 | |a Solinsky, Christine M |e verfasserin |4 aut | |
| 700 | 1 | |a Vargo, Dennis L |e verfasserin |4 aut | |
| 700 | 1 | |a Winkelmayer, Wolfgang C |e verfasserin |4 aut | |
| 700 | 1 | |a Chertow, Glenn M |e verfasserin |4 aut | |
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