Researchers, led by Jonathan Barratt, PhD, FRCP, conducted a study to examine the safety of roxadustat in patients with non-dialysis-dependent (NDD) or incident dialysis dialysis-dependent (ID-DD) chronic kidney disease (CKD). Study results were reported online in Advances in Therapy [doi:10.1007/s12325-023-02433-0].
The researchers pooled and evaluated safety results from four phase 3 randomized, open-label studies that compared roxadustat to an erythropoiesis-stimulating agent (ESA) in men and women with NDD or ID-DD CKD with anemia. The end points of interest were time to major cardiovascular event (MACE+). MACE was defined as myocardial infarction, stroke, and all-cause mortality; MACE + was defined as MACE plus congestive heart failure or unstable angina requiring hospitalization. Other end points were all-cause mortality, and treatment-emergent adverse events (TEAEs). MACE and MACE+ were evaluated for noninferiority at 1.8- and 1.3-margins using hazard ratios (HRs) and 95% CIs. TEAES were descriptively summarized.
The study cohort included 2142 patients; of those, 1083 received roxadustat and 1059 received an ESA. Roxadustat was comparable to ESA for the risk of MACE (HR, 0.79; 95% CI, 0.61-1.02), MACE+ (HR, 0.78; 95% CI, 0.62-0.98), and all-cause mortality (HR, 0.78; 95% CI, 0.57-1.05). The two groups were similar in TEAEs, including any TEAE (incidence rate [IR] per 100 patient-exposure years, 56.1 vs 53.5); TEAEs leading to study drug discontinuation (IR per 100 patient-exposure years 6.7 vs 5.1); and TEAEs leading to death (IR per 100 patient-exposure years 6.9 vs 7.4).
In summary, the authors said, “There was no evidence of increased risk of cardiovascular events or mortality with roxadustat compared with ESA in patients with anemia who have NDD or ID-DDD CKD. Although TEAEs occurred commonly in both the roxadustat and ESA groups, patients infrequently discontinued the study drug because of an adverse event.”
