#214 Responsiveness to roxadustat in non-dialysis chronic kidney disease patients with anemia by baseline iron status: a secondary analysis of the ROXSTAR registry

Abstract Background and Aims The ROXSTAR Registry (ChiCTR2100046322) is a phase 4, multicenter study conducted in China to evaluate the long-term safety and effectiveness of a 52-week roxadustat treatment in both dialysis and non-dialysis (ND) chronic kidney disease (CKD) patients with anemia. This study enrolled 2021 patients with various comorbidities, including iron deficiency (ID), reflecting real-world clinical practice. This secondary analysis aimed to assess anemia correction and hemoglobin (Hb) target achievement in ND-CKD patients stratified by baseline iron status. Method This secondary analysis utilized data from the ROXSTAR Registry, including ND-CKD patients who received roxadustat and had at least one post-baseline Hb measurement. Oral supplemental iron could be administered at any time according to clinical practice. Intravenous iron was administered if clinically indicated per investigator's judgement. Outcomes included the proportion of patients achieving mean Hb levels within 100–130 g/L, changes from baseline (CFB) in Hb over weeks 24–52, CFB in iron metabolism parameters (serum ferritin [SF], transferrin saturation [TSAT], serum iron, total iron binding capacity [TIBC], transferrin), and weekly roxadustat dosage, stratified into three baseline iron subgroups: iron repletion (SF≥100 µg/L and TSAT≥20%), absolute ID (SF<100 µg/L and TSAT <20%), and non-absolute ID (SF≥100 µg/L and TSAT<20% or SF <100 µg/L and TSAT≥20%). Results A total of 490 ND-CKD patients were analyzed (iron repletion: 186 [38.0%]; absolute ID: 99 [20.2%]; non-absolute ID: 205 [41.8%]). The absolute ID group had a higher proportion of females (78.8%). Overall baseline mean Hb was 95.3±12.2 g/L (iron repletion: 97.1±11.5 g/L; absolute ID: 91.3±11.9 g/L; non-absolute ID: 95.7±12.7 g/L). The proportion of patients with elevated C-reactive protein was higher in the absolute ID (18.2%) and non-absolute ID (17.6%) groups, compared to the iron repletion group (10.2%) (Table 1). Patients with absolute ID showed the greatest Hb improvement and the highest proportion achieving target Hb levels over weeks 24–52 (20.7 [95% CI: 17.5, 23.8] g/L; 88.5% [95% CI: 81.4%, 95.7%]), compared to the iron repletion 13.8 [95% CI: 11.8, 15.7] g/L; 83.5% [95% CI: 77.4%, 89.5%] and the non-absolute ID group (15.5 [95% CI: 13.5, 17.4] g/L; 83.9% [95% CI: 77.9%, 89.8%]). During treatment, 54.7% of patients received iron therapy (iron repletion: 52.2%; absolute ID: 59.6%; non-absolute ID: 54.6%). SF & TSAT increased in the absolute ID groups (CFB: 14.9 µg/L & 7.8% at week 24, 24.4 µg/L & 8.1% at week 52), contrasting with trends in the other groups. Serum iron, TIBC and transferrin level increased across all groups (Table 2). Roxadustat mean weekly dose was lower in the iron repletion group (195.9 ± 87.0 mg), compared to the absolute ID (237.7 ± 92.1 mg) and non-absolute ID (211.5 ± 80.8 mg) groups. In the iron repletion group, roxadustat weekly dose started at 239.9 ± 71.7 mg, gradually decreased to 168.0 ± 97.1 mg by weeks 24, then increased to 200.0 ± 106.6 mg by week 52. In contrast, the absolute ID group started at 242.3 ± 68.6 mg, increased to 273.0 ± 91.8 mg by week 12, then slightly decreased to 217.4 ± 111.5 mg by week 52. Conclusion Roxadustat effectively corrected anemia and maintained target Hb levels in ND-CKD patients across all baseline iron statuses, demonstrating its utility in real-world settings. Notably, even in patients with absolute ID, roxadustat improved Hb level and iron utilization when combined with oral supplemental iron.