#1194 Roxadustat in ESA converted patients with anemia of chronic kidney disease on dialysis: a secondary analysis of ROXSTAR Registry

Abstract

Abstract Background and Aims Anemia is associated with increased morbidity & mortality in chronic kidney disease (CKD) patients. Around 20% of patients experience erythropoiesis-stimulating agent (ESA) hypo-responsiveness and can't achieve hemoglobin (Hb) treatment target even with a high dose. Higher ESA dose is associated with undesirable outcomes. Roxadustat has demonstrated efficacy and safety in ESA converted CKD anemia patients. We conduct this secondary analysis of ROXSTAR registry (ChiCTR2100046322) to evaluate the Hb response to roxadustat in ESAs converted dialysis-dependent (DD) patients with prior weekly ESA dose ≥10000 U and <10000 U respectively. Method This study used existing data collected in the ROXSTAR Registry. DD patients converted from ESA treatment who received at least one dose of roxadustat, and had at least one post baseline Hb were included. We described the Hb response to roxadustat treatment in patients converted from higher ESA dose (≥10,000 U per week) and from lower ESA dose (<10,000 U per week) at enrollment. The changes from baseline to week 12 & week 24 in Quality of Life (QoL) assessed by SF-36 Vitality & Physical Function subscales, and Rapid Assessment of Physical Activity (RAPA) Strength & Flexibility scores were also analyzed respectively. Results Total 666 ESA converted DD patients were included. For the higher ESA dose group, there were 426 patients (257 male [60.3%]) with a mean (standard deviation [SD]) age of 49.5 [13.1] years, the median (mix, max) dialysis duration was 31.7 (0.2, 307.8) months. For the lower ESA dose group, 240 patients (141 male [58.8%]) with a mean age of 49.7 [13.0] years were enrolled, and median dialysis duration was 36.4 (0.4, 266.1) months. The mean baseline Hb was 98.0 (14.5) g/L in the higher ESA dose group and 102.2 (12.6) g/L in the lower ESA dose group. The median prior weekly ESA dose was 10000 (10000, 50000) U and 6000.0 (300, 9000) U in higher & lower ESA dose groups (Table 1). Mean weekly roxadustat dose during the first 12 weeks (correction phase) was maintained around 300 mg and then decreased to around 260 mg during 12-52 weeks (maintenance phase) for the higher ESA dose group; the dose started from around 300 mg and decreased to 270 mg during the correction phase and then gradually decreased to around 230 mg during the maintenance phase in the lower ESA dose group. The mean Hb change from baseline averaged over weeks 24-36 & 36-52 was 12.1 [95% CI: 10.5, 13.7] g/L & 12.3 [95% CI: 10.7, 13.9] g/L for the higher ESA dose group and 9.9 [95% CI: 8.0, 11.8] g/L & 10.2 [95% CI: 8.3, 12.1] g/L for the lower ESA dose group, respectively. The proportion (%) of patients with mean Hb ≥100 g/L at the same period were 82.3% [95% CI: 78.1%, 86.6%] & 83.6% [95% CI: 79.3%, 87.9%] in the higher ESA dose group and 88.4% [95% CI: 83.6%, 93.1%] & 89.0% [95% CI: 84.3%, 93.7%] in the lower ESA dose group. There was no clinical meaningful change of QoL observed in either group. Conclusion ESA-converted DD patients responded well to roxadustat in terms of anemia correction and Hb maintenance to treatment target, regardless of prior ESA dose. Similar starting doses of roxadustat were used for both groups and then gradually decreased during the maintenance phase (week 12-52) compared to the correction phase (week 1-12) while the magnitude of dose decrease was greater in the lower ESA dose group.