Efficacy and Safety of Roxadustat in Patients with CKD: Pooled Analysis by Baseline Inflammation Status

Background/Objectives: Inflammation may contribute to hyporesponsiveness to erythropoiesis-stimulating agents (ESAs) and is often present in patients with chronic kidney disease (CKD). Roxadustat is approved in multiple countries for the treatment of anemia of CKD. This pooled analysis evaluated the efficacy and safety of roxadustat in patients with dialysis-dependent (DD) or non-dialysis-dependent (NDD) CKD by inflammation status. Methods: Data from five studies comparing roxadustat versus ESAs were pooled by patient populations in this analysis (NDD: DOLOMITES; DD: ROCKIES, SIERRAS, HIMALAYAS, PYRENEES). The mean change from baseline in hemoglobin levels to Weeks 28-52 and mean weekly dose of roxadustat or ESA at Week 24 were assessed by baseline inflammation levels (determined by high-sensitivity C-reactive protein [hsCRP] levels, divided into quintiles). Safety data were summarized descriptively. Results: In total, 613 patients with NDD CKD (roxadustat n = 320; ESA n = 293) and 4072 patients with DD CKD (roxadustat n = 2022; ESA n = 2050) were evaluated. Roxadustat increased hemoglobin levels in a manner similar to ESAs, independent of baseline inflammation status. In both the NDD and DD populations, roxadustat doses did not increase at Week 24 in patients with higher hsCRP levels at baseline. Patients with high baseline hsCRP levels required greater ESA doses at Week 24 compared with patients who had lower baseline hsCRP levels in both patient populations. The incidence rates of treatment-emergent adverse events were generally comparable with those of roxadustat and ESA across hsCRP quintiles in both the NDD and DD populations. Conclusions: Roxadustat addresses the multiple causes of anemia of CKD, regardless of inflammatory status, without requiring dose increases.