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.