Dataset Information

The efficacy of Roxadustat for the treatment of anemia in dialysis dependent chronic kidney disease patients: an updated systematic review and meta-analysis of randomized clinical trials.

ABSTRACT:

Background

Anemia is a common complication in chronic kidney disease (CKD) with increased morbidity and mortality. Recently published RCTs were conducted to compare the effect of the new medication roxadustat (ROX) with erythropoiesis-stimulating agent (ESA) in dialysis-dependent CKD (DD-CKD) patients. Our article aimed to meta-analyze published RCTs to investigate the efficacy and safety of ROX for anemia in DD-CKD patients and update the effect of the new studies on overall analysis with subsequent impact on management.

Methods

Electronic databases (PubMed, EMBASE, Scopus, Web of Science, Cochrane Central, and Google Scholar) were searched systematically from inception to July 2021 by using this search term (Roxadustat OR ASP1517 OR FG4592 OR "FG-4592") AND (kidney OR renal) AND (Anemia). We only included randomized control trials (RCTs) that reported the primary outcome of change in hemoglobin (Hb) level and iron utilization parameters, including ferritin, serum iron, TSAT, TIBC, transferrin, and hepcidin.

Results

Ten RCTs were finally included with 3031 patients in the ROX group and 2737 patients in the control group. ROX was associated with increase in Hb level (SMD: 0.2; 95% CI: 0.02, 0.39; P=0.03), TIBC (SMD: 0.79; 95% CI: 0.61, 0.98; P<0.00001), serum iron (SMD: 0.27; 95% CI: 0.18, 0.36; P<0.00001), transferrin (SMD: 0.98; 95% CI: 0.81, 1.15; P<0.00001) and decrease in hepcidin (SMD: -15.53; 95% CI: -28.07, -3.00; P<0.02) when compared with control group. There was no difference between ROX and the control group regarding ferritin level and TSAT. Sensitivity analysis by removing the most recent studies, Chen et al. or Hou et al. did not show significant difference in regard to change in Hb level. There was no difference between both groups regarding the serious side effects. However, ROX showed higher TEAEs when compared to the control group (RR: 1.03; 95% CI: 1.01, 1.05; P=0.002).

Discussion

Our updated meta-analysis concluded that ROX increased Hb level and improved iron utilization parameters in DD-CKD patients, but ROX was associated with higher TEAEs. Our results support the use of ROX for DD-CKD patients with anemia. However, higher-quality RCTs are still needed to confirm the results of our review.

SUBMITTER: Abdelazeem B

PROVIDER: S-EPMC8743719 | biostudies-literature |

REPOSITORIES: biostudies-literature

ACCESS DATA

Similar Datasets

Project description:IntroductionThis integrated phase 3 analysis examined efficacy and cardiovascular safety for roxadustat vs erythropoiesis-stimulating agents (ESAs) in dialysis-dependent patients.MethodsEfficacy and safety results from four phase 3, randomized, open-label studies comparing roxadustat to ESAs (PYRENEES, SIERRAS, HIMALAYAS, ROCKIES) in dialysis-dependent patients with anemia of chronic kidney disease (CKD) were evaluated by study, pooled population and in two subgroups: incident dialysis and stable dialysis. The primary efficacy endpoint per study was hemoglobin change from baseline (CFB) to weeks 28-36 using least-squares mean difference (LSMD) without rescue therapy. Pooled safety endpoints included time to major adverse cardiovascular event (MACE; myocardial infarction, stroke, and all-cause mortality [ACM]) and MACE+ (MACE plus congestive heart failure or unstable angina requiring hospitalization), ACM, and treatment-emergent adverse events (TEAEs). MACE and MACE+ were evaluated for non-inferiority at 1.8 and 1.3 margins using hazard ratios (HRs) and 95% confidence intervals (CIs). TEAEs were descriptively summarized.ResultsIn total, 4714 patients were randomized (2354 roxadustat; 2360 ESA). Hemoglobin CFB to weeks 28-36 achieved non-inferiority for roxadustat vs ESA in each study. Roxadustat was non-inferior to ESA for risks for MACE and MACE+ in the entire cohort (MACE: HR 1.09, 95% CI 0.95-1.26; MACE+ : HR 0.98, 95% CI 0.86-1.11) and similar to the incident dialysis and stable dialysis subgroups; ACM results were consistent with MACE and MACE+ (HR 1.13, 95% CI 0.95-1.34). TEAEs were generally comparable between groups.ConclusionRoxadustat improved hemoglobin similarly to ESA while demonstrating comparable cardiovascular and overall safety profiles in a wide spectrum of dialysis-dependent patients with anemia of CKD. Roxadustat represents an oral alternative to ESAs for achieving a target hemoglobin for anemia of CKD in dialysis-dependent patients.

Project description:Background and objectivesWe evaluated the efficacy and cardiovascular safety of roxadustat versus placebo by analyzing data pooled from three phase 3 studies of roxadustat in patients with non-dialysis-dependent CKD and CKD-related anemia.Design, setting, participants, & measurementsIn the three phase 3, double-blind studies of roxadustat versus placebo evaluating the treatment of CKD-related anemia in patients not requiring dialysis, the primary efficacy end point was mean change from baseline in hemoglobin averaged over weeks 28-52, regardless of rescue therapy. The primary cardiovascular safety end point was a composite measure of major adverse cardiovascular events (MACE; all-cause mortality, myocardial infarction, stroke). MACE plus (MACE+; MACE plus unstable angina and heart failure requiring hospitalization) and all-cause mortality were key secondary safety end points. These safety end points were adjudicated.ResultsA total of 4277 patients with non-dialysis-dependent CKD were randomized (roxadustat, n=2391; placebo, n=1886). Baseline characteristics were comparable between groups; the mean (SD) hemoglobin was 9.1 (0.7) g/dl and mean eGFR was 20 (12) ml/min per 1.73 m2. Patients treated with roxadustat versus those treated with placebo showed a mean change from baseline in hemoglobin averaged over weeks 28-52, regardless of rescue therapy, of 1.9 versus 0.2 g/dl, a treatment difference of 1.7 (95% confidence interval [95% CI], 1.7 to 1.8). Roxadustat reduced the need for red blood cell transfusion in the first 52 weeks versus placebo (6.1 versus 20.4 per 100 patient-exposure years, respectively; hazard ratio [HR], 0.26; 95% CI, 0.21 to 0.32). There were no increased risks of MACE (HR, 1.10; 95% CI, 0.96 to 1.27), MACE+ (HR, 1.07; 95% CI, 0.94 to 1.21), all-cause mortality (HR, 1.08; 95% CI, 0.93 to 1.26), or individual MACE+ components in patients treated with roxadustat versus those treated with placebo.ConclusionsRoxadustat was more effective than placebo at increasing hemoglobin in patients with non-dialysis-dependent CKD and anemia, while decreasing transfusion rate and being noninferior to placebo with respect to risk of MACE.Clinical trial registry name and registration numberA Study of FG-4592 for the Treatment of Anemia in Chronic Kidney Disease Patients Not Receiving Dialysis, NCT01750190; Roxadustat in the Treatment of Anemia in Chronic Kidney Disease Patients Not Requiring Dialysis (ALPS), NCT01887600; Safety and Efficacy Study of Roxadustat to Treat Anemia in Patients With Chronic Kidney Disease (CKD), Not on Dialysis, NCT02174627.