Safety of Roxadustat in Chronic Kidney Disease Patients: An Updated Systematic Review and Meta-Analysis

Background/Objectives: Roxadustat is a new treatment for the anemia of chronic kidney disease (CKD) that has comparable efficacy to erythropoietic-stimulating agents (ESAs), with the advantage of oral administration and increased iron bioavailability. It appears to be a safe treatment in terms of the development of major adverse cardiovascular events (MACEs); however, its long-term safety has not been fully evaluated. In this meta-analysis we evaluate its safety in dialysis-dependent (DD) and non-dialysis-dependent (NDD) CKD patients, considering the comparator used and treatment duration. Methods: The safety of Roxadustat was assessed based on the incidence of serious (SAEs) and non-serious adverse events (AEs). A random-effects method was used to estimate the odds ratios (ORs) and their 95% CIs. Results: Fifteen different randomized controlled clinical trials were included, with a total of 10,284 patients with CKD stages 3-5 treated with Roxadustat, 5604 on dialysis and 4680 not on dialysis. The overall incidence of AEs in the Roxadustat group did not change significantly (OR = 1.13; 1.00-1.27); however, the incidence of SAEs was significantly higher than in the control group (OR = 1.13; 1.04-1.23). Specifically, the incidence of hypertension (OR = 1.39; 1.13-1.73) and hyperkalemia (OR = 1.31; 1.02-1.69) was higher in the Roxadustat group than in the placebo group of NDD patients. All AEs except MACEs and hyperkalemia increased with treatment > 30 weeks. No differences were found in the incidence of any adverse effects studied compared with ESAs. Conclusions: Roxadustat is associated with an increased risk of SAEs, including hypertension and hyperkalemia in NDD patients. Therefore, monitoring potassium levels and blood pressure is recommended in these patients.