#2959 EFFICACY AND SAFETY OF ROXADUSTAT IN PATIENTS WITH ANEMIA OF DIALYSIS-DEPENDENT CKD WITH OR WITHOUT INFLAMMATION: A POOLED ANALYSIS OF 4 PHASE 3 STUDIES

Abstract

Abstract Background and Aims Erythropoiesis-stimulating agents (ESAs) are commonly used to treat anemia of chronic kidney disease (CKD). ESA hyporesponsiveness is prevalent in a significant portion of patients with CKD, especially those with end-stage renal disease on dialysis. Inflammation has been reported to contribute to ESA hyporesponsiveness and is associated with poor outcomes in patients with CKD. Roxadustat, an oral medication, is a hypoxia-inducible factor prolyl hydroxylase inhibitor that has previously demonstrated efficacy in patients with anemia of CKD. This pooled analysis evaluated the efficacy and safety of roxadustat in correcting hemoglobin (Hb) levels in subgroups of patients with dialysis-dependent (DD) CKD with or without inflammation at baseline. Method Data for this analysis were pooled from four phase 3, randomized, open-label, active comparator−controlled studies (HIMALAYAS [NCT02052310], ROCKIES [NCT02174731], PYRENEES [NCT02278341], SIERRAS [NCT02273726]) in patients with DD CKD. Outcomes evaluated were mean Hb change from baseline to Weeks 28−52 and mean weekly roxadustat dose (mg/kg) at Week 24 in patients with or without baseline inflammation (as determined by high-sensitivity C-reactive protein [hsCRP] level, divided into quintiles). Data were analyzed with an analysis of covariance model with baseline Hb as a covariate. Adjusted least-squares means, their difference, and corresponding confidence intervals were generated from datasets where missing data were imputed using missing at random-based multiple imputation, by treatment group, with baseline Hb, cardiovascular/cerebrovascular/thromboembolic history, geographical region (United States vs non-United States) and incident vs stable dialysis (≤4 vs >4 months) as predictor variables. Safety data were summarized descriptively. Results In total, 4072 patients with DD CKD (roxadustat N = 2022; ESA N = 2050) were evaluated. At baseline, mean Hb levels (g/dL [SD]) were similar in the roxadustat (9.80 [1.29]) and ESA (9.83 [1.29]) groups, regardless of baseline hsCRP levels (roxadustat hsCRP quintiles 1−5: 9.72 [1.43], 9.78 [1.27], 9.80 [1.32], 9.90 [1.18], and 9.79 [1.23], respectively; ESA hsCRP quintiles 1−5: 9.75 [1.34], 9.92 [1.23], 9.90 [1.23], 9.96 [1.23], and 9.62 [1.38], respectively). Hb change from baseline was greater in patients treated with roxadustat compared with ESA, regardless of baseline hsCRP levels (Fig. 1). At Week 24, patients with higher baseline hsCRP levels did not require higher doses of roxadustat compared to patients with lower baseline hsCRP levels (Fig. 2). The overall percentages of patients with at least one treatment-emergent adverse event were similar for patients treated with roxadustat (hsCRP quintiles 1−5: 86.7, 88.1, 86.6, 88.7, and 90.0, respectively) or ESA (hsCRP quintiles 1−5: 83.5, 84.6, 90.5, 88.2, and 87.9, respectively) across hsCRP quintiles. Conclusion In patients with anemia of DD CKD, roxadustat increased Hb levels without requiring increased doses of roxadustat in patients with or without baseline inflammation. Results from the current analysis suggest that roxadustat is effective, with a comparable safety profile to ESA, regardless of inflammation status.