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Clinical Trial
. 2024 May;28(5):391-403.
doi: 10.1007/s10157-023-02432-z. Epub 2024 Mar 26.

Factors affecting responsiveness of vadadustat in patients with anemia associated with chronic kidney disease: a post-hoc subgroup analysis of Japanese phase 3 randomized studies

Masaomi Nangaku  1 , Kiichiro Ueta  2 , Kenichi Nishimura  3 , Kazuyo Sasaki  3 , Takafumi Hashimoto  3
Affiliations
Clinical Trial

Factors affecting responsiveness of vadadustat in patients with anemia associated with chronic kidney disease: a post-hoc subgroup analysis of Japanese phase 3 randomized studies

Masaomi Nangaku et al. Clin Exp Nephrol. 2024 May.

Abstract

Background: Vadadustat is an oral hypoxia-inducible factor prolyl hydroxylase inhibitor developed for treating anemia in chronic kidney disease (CKD). The purpose of this post-hoc analysis was to investigate the factors affecting the responsiveness to vadadustat in anemia patients with nondialysis-dependent (NDD) or hemodialysis-dependent (HDD) CKD in two Japanese phase 3 studies.

Methods: Of 151 and 162 patients enrolled in NDD-CKD and HDD-CKD studies, 136 and 140 patients, respectively, were included and divided into subgroups for the analysis. To assess vadadustat responsiveness, the resistance index was defined as the mean body weight-adjusted dose of vadadustat (mg/kg) at weeks 20-24 divided by the mean hemoglobin (g/dL) at weeks 20-24. Multivariate analysis was performed to identify the variables affecting the resistance index.

Results: Independent factors identified as determinants for better response to vadadustat were as follows: high baseline hemoglobin, low baseline eGFR, high week-20-24 ferritin, and CKD not caused by autoimmune disease/glomerulonephritis/vasculitis in NDD-CKD; and male sex, high baseline C-reactive protein, and low baseline erythropoiesis-stimulating agent resistance index (ERI) in HDD-CKD.

Conclusions: In this post-hoc analysis, several factors were identified as affecting the response to vadadustat. These results may provide useful information leading to an appropriate dose modification for vadadustat.

Clinical trial registration: NCT03329196 (MT-6548-J01) and NCT03439137 (MT-6548-J03).

Keywords: Anemia; Chronic kidney disease; Hypoxia-inducible factor prolyl hydroxylase inhibitor; Responsiveness; Subgroup analysis; Vadadustat.

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Conflict of interest statement

M. Nangaku received honoraria, advisory fees, or research funding from Astellas Pharma Inc., AstraZeneca K.K., Bayer Yakuhin, Ltd, Nippon Boehringer Ingelheim Co., Ltd., Chugai Pharmaceutical Co., Ltd., Daiichi Sankyo Co., Ltd., GlaxoSmithKline K.K., Japan Tobacco Inc., Kyowa Kirin Co., Ltd., Takeda Pharmaceutical Co., Ltd., Torii Pharmaceutical Co., Ltd., and Mitsubishi Tanabe Pharma Corporation. K. Ueta, K. Nishimura, K. Sasaki, and T. Hashimoto are employees of Mitsubishi Tanabe Pharma Corporation.

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References

    1. Astor BC, Muntner P, Levin A, Eustace JA, Coresh J. Association of kidney function with anemia: the Third National Health and Nutrition Examination Survey (1988–1994) Arch Intern Med. 2002;162(12):1401–1408. doi: 10.1001/archinte.162.12.1401. - DOI - PubMed
    1. McClellan W, Aronoff SL, Bolton WK, Hood S, Lorber DL, Tang KL, et al. The prevalence of anemia in patients with chronic kidney disease. Curr Med Res Opin. 2004;20(9):1501–1510. doi: 10.1185/030079904x2763. - DOI - PubMed
    1. Markham A. Vadadustat: First Approval. Drugs. 2020;80(13):1365–1371. doi: 10.1007/s40265-020-01383-z. - DOI - PubMed
    1. Dhillon S. Roxadustat: First Global Approval. Drugs. 2019;79(5):563–572. doi: 10.1007/s40265-019-01077-1. - DOI - PubMed
    1. Dhillon S. Daprodustat: First Approval. Drugs. 2020;80(14):1491–1497. doi: 10.1007/s40265-020-01384-y. - DOI - PMC - PubMed

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