Roxadustat for anemia in patients with end-stage renal disease incident to dialysis

Abstract

Background We evaluated the efficacy and safety of roxadustat vs. epoetin alfa for the treatment of chronic kidney disease (CKD) related anemia in patients new to dialysis. Methods This was a phase 3, open-label, epoetin alfa-controlled trial. Eligible adults were on hemodialysis/peritoneal dialysis for ≥2 weeks and ≤4 months before randomization and had mean hemoglobin ≤10.0 g/dL. Primary endpoints were mean hemoglobin (g/dL) change from baseline averaged over weeks 28–52 regardless of rescue therapy (non-inferiority criterion: lower limit of 95% CI for treatment difference > −0.75) and percentage of patients achieving a hemoglobin response between weeks 1–24 censored for rescue therapy (non-inferiority margin for between-group difference: −15%). Adverse events were monitored. Results The intention-to-treat population included patients randomized to roxadustat (n = 522) or epoetin alfa (n = 521). Mean (SD) hemoglobin changes from baseline averaged over weeks 28–52 were 2.57 (1.27) and 2.36 (1.21) in the roxadustat and epoetin alfa groups. Roxadustat was non-inferior (least-squares mean difference: 0.18 [95% CI: 0.08, 0.29]) to epoetin alfa. Percentages of patients with a hemoglobin response were 88.2% and 84.4% in the roxadustat and epoetin alfa groups. Roxadustat was non-inferior to epoetin alfa (treatment-group difference: 3.5% [95% CI: −0.7%, 7.7%]). Adverse event rates were comparable between treatment groups. Conclusions Roxadustat was efficacious for correcting and maintaining hemoglobin levels compared to epoetin alfa. Roxadustat had an acceptable safety profile.

Roxadustat for the treatment of anaemia in chronic kidney disease patients not on dialysis: a Phase 3, randomized, open-label, active-controlled study (DOLOMITES)

“…Roxadustat was superior to DA for LDL lowering from BL to Weeks 12–28, which corroborates prior data in NDD [ 14 , 15 ] and DD [ 8 , 12 ] CKD patients. LDL levels remained lower with roxadustat throughout the study.…”

Safe and Effective Treatment for Anemic Patients With Chronic Kidney Disease: An Updated Systematic Review and Meta-Analysis on Roxadustat

“…The total number of patients was 10,189: 4,810 DD-CKD patients (seven trials) and 5,379 NDD-CKD patients (eight trials). Of all the DD-CKD patient trials, four trials compared roxadustat with epoetin alfa Chen et al (2017), Chen et al (2019a), NCT02174731 (2020), Provenzano et al (2021), two trials compared roxadustat with darbepoetin alfa NCT01888445 (2018), Akizawa et al (2020a) and one trial compared roxadustat with both of above mentioned ESAs NCT02278341 (2019), and they were all not blinded except for two trials (NCT01888445, 2018; Akizawa et al, 2020a). In the NDD-CKD patient trials, placebos were used as control except in one trial NCT02021318 (2021), in which darbepoetin alfa was administrated as the comparator.…”

“…The evaluation of the included RCTs through Cochrane Collaboration's tool showed that high risk of bias mainly concentrated in DD-CKD patient trials, involving the blinding of the participants, personnel and outcome assessment (for open-label study) (Chen et al, 2017;Chen et al, 2019a;NCT02278341, 2019;NCT02174731, 2020;Provenzano et al, 2021). Defects in random sequence generation and allocation concealment also introduced some unclear risk of bias.…”

“…Roxadustat Increased the Level of Hemoglobin in Non-Dialysis-Dependent Chronic Kidney Disease Patients With Elevated C-reactive Protein Levels Inflammation, which causes iron retention, increased hepcidin formation and impaired erythroid progenitor proliferation was believed as a major contributing factor to anemia (Macdougall et al, 2016;Weiss et al, 2019). In order to assess the influence of inflammation on the effect of roxadustat, we extracted Hb changes in subjects with baseline CRP > ULN from six trials (Chen et al, 2019a;Akizawa et al, 2019c;NCT02174731, 2020;Coyne et al, 2021;Fishbane et al, 2021;Provenzano et al, 2021) (four trials for DD-CKD patients, two trials for NDD-CKD patients). The pooled results showed that for patients with baseline CRP upper than ULN, there was a significant rise of Hb level with the use of roxadustat compared with ESAs and placebo (WMD: 0.63; 95% CI: 0.09-1.17; p 0.02; with heterogeneity [p < 0.00001]; Figure 5 and Table 3).…”

“…In addition, the duration of the studies enrolled in previous meta-analyses was relatively short, with a maximum follow-up of 26 weeks. Recently, the results of five large phase 3 clinical trials Akizawa et al (2020a), Coyne et al (2021), Fishbane et al (2021), Provenzano et al (2021), Shutov et al (2021) of roxadustat were released, so we updated the meta-analysis. Randomized controlled trials that assessed the efficacy (hemoglobin levels and response) and safety (treatment-emergent adverse events) of roxadustat in DD-CKD and NDD-CKD anemia patients comparing with ESAs or placebo were retriedved with an aim to generate a robust conclusion on the effect of and safety of roxadustat.…”