Pooled Analysis of Roxadustat for Anemia in Patients With Kidney Failure Incident to Dialysis
Authors: Tyson T Lee
Steven Fishbane
Kin-Hung Peony Yu
Ming Zhong
John Houghton
Dustin J Little
Khalil G Saikali
Robert Provenzano
Lynda Szczech
Thomas B Neff
Robert Leong
Lars Frison
Mark T Houser
Journal: Kidney International Reports (2021)
Discipline: CLINICAL MEDICINE
Keywords: anemia; chronic kidney disease; dialysis; roxadustat.
Affiliations: School of Medicine, Wayne State University, Detroit, Michigan, USA., Department of Medicine, Donald and Barbara Zucker School of Medicine at Hofstra/Northwell, Great Neck, New York, USA., FibroGen, Inc., San Francisco, California, USA., AstraZeneca, Gaithersburg, Maryland, USA., AstraZeneca, Mölndal, Sweden.

Abstract:  Introduction: Erythropoiesis-stimulating agents are associated with increased cardiovascular risk when higher doses are used toward higher hematocrit targets. Patients new to dialysis are at higher risk for morbidity and mortality. Systematic evaluation of this population was predefined in the roxadustat clinical development program. Roxadustat is a hypoxia-inducible prolyl hydroxylase inhibitor. Methods: Data were pooled from 3 phase 3, randomized, open-label, active-controlled trials. Eligible adults had kidney failure and initiated dialysis for 2 weeks to ≤ 4 months prior to randomization to roxadustat or epoetin alfa. Efficacy was assessed as mean change in hemoglobin from baseline averaged over weeks 28 to 52, regardless of rescue therapy. Key cardiovascular safety endpoints were major adverse cardiovascular events (MACE; all-cause mortality [ACM], myocardial infarction, and stroke), and MACE+ (MACE plus unstable angina or congestive heart failure requiring hospitalization), and ACM. Results: This study included 1530 patients with kidney failure incident to dialysis. Mean (SD) changes in hemoglobin from baseline averaged over weeks 28 to 52, regardless of rescue therapy, were 2.12 (1.45) versus 1.91 (1.42) g/dl in the roxadustat and epoetin alfa groups (least-squares mean difference: 0.22; 95% CI, 0.05 to 0.40; P = 0.0130). Risks of MACE and MACE+ were lower in the roxadustat group (hazard ratio [HR], 0.70; 95% CI, 0.51 to 0.96) than the epoetin alfa group (HR, 0.66; 95% CI, 0.50 to 0.89); the HR for ACM was 0.76 (95% CI, 0.52 to 1.11). Conclusion: Roxadustat was at least as efficacious as epoetin alfa. Roxadustat had a lower risk of MACE/MACE+ in patients new to dialysis. 

Retracted: Yes

PubPeer comments:
 Copy pasted from https: retractionwatch.com 2021 05 11 clinical-trial-paper-that-made-anemia-drug-look-safer-than-it-is-will-be-retracted :  (...) a spokesperson for Elsevier, the journalu2019s publisher, told Retraction Watch this week that the paper will be retracted and that the u201cauthors will be given the opportunity to resubmit a corrected version.u201d (...) , 
 Retraction, February 2022: https: www.kireports.org article S2468-0249(22)01131-7 fulltext#relatedArticles  This article has been retracted: please see Elsevier Policy on Article Withdrawal (http: www.elsevier.com locate withdrawalpolicy). There were significant concerns about the analysis included in the original manuscript, including deviations from the proposed analytic plan that were only identified after publication. The authors did not address these concerns to the satisfaction of the editors to meet the journalu2019s standard for scientific rigor. Furthermore, there was an absence of consensus among the authors about the nature extent of the corrections. For these reasons, the publication has been retracted. ,