The efficacy and safety of roxadustat for the treatment of anemia in non-dialysis dependent chronic kidney disease patients: An updated systematic review and meta-analysis of randomized clinical trials

McLaren Health Care, Flint, Michigan, United States of America. Michigan State University, East Lansing, Michigan, United States of America. Faculty of Medicine, Cairo University, Cairo, Egypt. Faculty of Medicine, Alexandria University, Alexandria, Egypt. Faculty of Medicine for Girls, Al-Azher University, Cairo, Egypt. Louisiana State University Health Sciences Center, Monroe, Louisiana, United States of America. The Ohio State University, Columbus, Ohio, United States of America.

PloS one. 2022;17(4):e0266243
PICO Summary

Population

People with non-dialysis-dependent chronic kidney disease who took part in randomised controlled trials (RCTs) identified by a systematic review (n= 5,621, 9 RCTs).

Intervention

Roxadustat at various doses (ROX, n= 3,175).

Comparison

Placebo or control treatment [Darbepoetin Alfa], (n= 2,446).

Outcome

When compared the control group, ROX increased Haemoglobin level significantly (standardised mean difference [SMD]: 1.65; 95% CI: 1.08, 2.22) and improved iron utilization parameters by decreasing ferritin (SMD: -0.32; 95% CI: -0.51, -0.14), transferrin saturation (SMD: -0.19; 95% CI: -0.32, -0.07), and hepcidin (SMD: -0.74; 95% CI: -1.09, -0.39) and increasing total iron binding capacity (SMD: 0.99; 95% CI: 0.76, 1.22) and transferrin (SMD: 1.20; 95% CI: 0.70, 1.71). As for safety, ROX was associated with higher serious adverse effects (RR: 1.07; 95% CI: 1.01, 1.13), deep venous thrombosis (RR: 3.80; 95% CI: 1.5, 9.64), and hypertension (RR: 1.37; 95% CI: 1.13, 1.65).
Abstract
BACKGROUND Roxadustat (ROX) is a new medication for anemia as a complication of chronic kidney disease (CKD). Our meta-analysis aims to evaluate the efficacy and safety of ROX, especially on the cardiovascular risks, for anemia in NDD-CKD patients. METHODS Electronic databases were searched systematically from inception to July 2021 to look for randomized control trials (RCTs) that evaluated ROX NDD-CKD patients. Hemoglobin level and iron utilization parameters, including ferritin, serum iron, transferrin saturation (TSAT), total iron-binding capacity (TIBC), transferrin, and hepcidin were analyzed for efficacy. Pooled risk ratios (RRs) and standardized mean differences (SMDs) were calculated and presented with their 95% confidential intervals (CIs). RESULTS Nine RCTs included a total of 3,175 patients in the ROX group and 2,446 patients in the control group. When compared the control group, ROX increased Hb level significantly (SMD: 1.65; 95% CI: 1.08, 2.22; P< 0.00001) and improved iron utilization parameters by decreasing ferritin (SMD: -0.32; 95% CI: -0.51, -0.14; P = 0.0006), TSAT (SMD: -0.19; 95% CI: -0.32, -0.07; P = 0.003), and hepcidin (SMD: -0.74; 95% CI: -1.09, -0.39; P< 0.0001) and increasing TIBC (SMD: 0.99; 95% CI: 0.76, 1.22; P< 0.00001) and transferrin (SMD: 1.20; 95% CI: 0.70, 1.71; P< 0.00001). As for safety, ROX was associated with higher serious adverse effects (RR: 1.07; 95% CI: 1.01, 1.13; P = 0.01), deep venous thrombosis (DVT) (RR: 3.80; 95% CI: 1.5, 9.64; P = 0.08), and hypertension (HTN) (RR: 1.37; 95% CI: 1.13, 1.65; P = 0.001). CONCLUSION We concluded that ROX increased Hb level and improved iron utilization parameters in NDD-CKD patients, but ROX was associated with higher serious adverse effects, especially DVT and HTN. Our results support the use of ROX for NDD-CKD patients with anemia. However, higher-quality RCTs are still needed to ensure its safety and risk of thrombosis.
Study details
Study Design : Systematic Review
Language : eng
Credits : Bibliographic data from MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine