Changes in Iron Availability with Roxadustat in Nondialysis- and Dialysis-Dependent Patients with Anemia of CKD.
Humans
Anemia
/ drug therapy
Epoetin Alfa
/ metabolism
Erythropoietin
/ metabolism
Ferritins
/ therapeutic use
Glycine
/ analogs & derivatives
Hemoglobins
/ analysis
Hepcidins
Iron
/ therapeutic use
Isoquinolines
Prolyl-Hydroxylase Inhibitors
/ therapeutic use
Renal Dialysis
Renal Insufficiency, Chronic
/ complications
Randomized Controlled Trials as Topic
Clinical Trials, Phase III as Topic
anemia
chronic kidney disease
hemoglobin
iron
roxadustat
Journal
Kidney360
ISSN: 2641-7650
Titre abrégé: Kidney360
Pays: United States
ID NLM: 101766381
Informations de publication
Date de publication:
29 09 2022
29 09 2022
Historique:
received:
11
03
2022
accepted:
29
06
2022
entrez:
17
10
2022
pubmed:
18
10
2022
medline:
19
10
2022
Statut:
epublish
Résumé
Roxadustat, a hypoxia-inducible factor prolyl hydroxylase inhibitor, increases hemoglobin by stimulating erythropoietin synthesis and improving iron availability through facilitation of iron uptake and/or release from stores. In this exploratory analysis, we assessed the effect of roxadustat treatment on laboratory parameters related to iron metabolism in patients with anemia of chronic kidney disease (CKD). Data were pooled from pivotal, randomized, phase 3 roxadustat trials: three placebo-controlled, double-blind trials in nondialysis-dependent (NDD) CKD and three open-label, active-comparator (epoetin alfa) trials in dialysis-dependent (DD) CKD. In this exploratory analysis, mean changes from baseline in hemoglobin, iron parameters, and hepcidin, and intravenous (iv) iron use were evaluated. Pooled results in NDD CKD and DD CKD patients are reported. Overall, 4277 patients with NDD CKD and 3890 patients with DD CKD were evaluated. Hemoglobin increases with roxadustat treatment were accompanied by increases in serum iron and total iron-binding capacity (TIBC) and decreases in serum ferritin and hepcidin from baseline through week 52. With epoetin alfa, the hemoglobin increase was accompanied by decreases in serum ferritin and hepcidin, but serum iron decreased, and there was no change in TIBC. With placebo, there were no changes in hemoglobin, iron parameters, or hepcidin. During treatment, iv iron use was reduced with roxadustat versus placebo and epoetin alfa. In patients with NDD CKD and DD CKD, roxadustat treatment is associated with increases in serum iron and TIBC, accompanied by reduced hepcidin and indicative of improved iron kinetics. Patients treated with roxadustat achieved target hemoglobin levels with less iv iron use versus comparators. Practitioners treating patients with anemia of CKD with roxadustat should consider its unique effects when interpreting iron parameters.
Sections du résumé
Background
Roxadustat, a hypoxia-inducible factor prolyl hydroxylase inhibitor, increases hemoglobin by stimulating erythropoietin synthesis and improving iron availability through facilitation of iron uptake and/or release from stores. In this exploratory analysis, we assessed the effect of roxadustat treatment on laboratory parameters related to iron metabolism in patients with anemia of chronic kidney disease (CKD).
Methods
Data were pooled from pivotal, randomized, phase 3 roxadustat trials: three placebo-controlled, double-blind trials in nondialysis-dependent (NDD) CKD and three open-label, active-comparator (epoetin alfa) trials in dialysis-dependent (DD) CKD. In this exploratory analysis, mean changes from baseline in hemoglobin, iron parameters, and hepcidin, and intravenous (iv) iron use were evaluated. Pooled results in NDD CKD and DD CKD patients are reported.
Results
Overall, 4277 patients with NDD CKD and 3890 patients with DD CKD were evaluated. Hemoglobin increases with roxadustat treatment were accompanied by increases in serum iron and total iron-binding capacity (TIBC) and decreases in serum ferritin and hepcidin from baseline through week 52. With epoetin alfa, the hemoglobin increase was accompanied by decreases in serum ferritin and hepcidin, but serum iron decreased, and there was no change in TIBC. With placebo, there were no changes in hemoglobin, iron parameters, or hepcidin. During treatment, iv iron use was reduced with roxadustat versus placebo and epoetin alfa.
Conclusions
In patients with NDD CKD and DD CKD, roxadustat treatment is associated with increases in serum iron and TIBC, accompanied by reduced hepcidin and indicative of improved iron kinetics. Patients treated with roxadustat achieved target hemoglobin levels with less iv iron use versus comparators. Practitioners treating patients with anemia of CKD with roxadustat should consider its unique effects when interpreting iron parameters.
Identifiants
pubmed: 36245647
doi: 10.34067/KID.0001442022
pii: 02200512-202209000-00010
pmc: PMC9528373
doi:
Substances chimiques
Epoetin Alfa
64FS3BFH5W
Erythropoietin
11096-26-7
Ferritins
9007-73-2
Glycine
TE7660XO1C
Hemoglobins
0
Hepcidins
0
Iron
E1UOL152H7
Isoquinolines
0
Prolyl-Hydroxylase Inhibitors
0
roxadustat
X3O30D9YMX
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
1511-1528Informations de copyright
Copyright © 2022 by the American Society of Nephrology.
Déclaration de conflit d'intérêts
S. Fishbane and P.E. Pergola have received research support and consulting fees from AstraZeneca. D.J. Little and S. Tham are employees of AstraZeneca. R. Leong and L. Szczech are former employees of FibroGen, Inc. C. Charytan has received research support from AstraZeneca and FibroGen, Inc.
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