EFFICACY OF ROXADUSTAT IN CHRONIC KIDNEY DISEASE PATIENTS NOT ON DIALYSIS WITH ANEMIA: SYSTEMATIC REVIEW AND META-ANALYSIS OF RANDOMIZED CONTROLLED TRIALS

Anemia is a common complication in patients with Chronic Kidney Disease (CKD), particularly in those not receiving dialysis. Roxadustat, a Hypoxia-Inducible Factor Prolyl Hydroxylase Inhibitor (HIF-PHI), has been investigated as a therapeutic option for anemia management in this population. This study aimed to evaluate the efficacy of Roxadustat compared to control interventions in Non-Dialysis-Dependent CKD (NDD-CKD) patients. A comprehensive literature search was conducted in Cochrane CENTRAL, Ovid Medline, PubMed, and Web of Science up to December 14, 2024. Randomized Controlled Trials (RCTs) directly comparing Roxadustat with a control group were included. Data were pooled using an inverse variance-weighted random-effects model. The primary efficacy outcome was the change in Hemoglobin (Hb) levels at weeks 24–28 and during follow-up. Subgroup analyses were performed based on the type of control intervention (Erythropoiesis-Stimulating Agents [ESAs] vs. placebo) and prior ESA use. A total of six RCTs, including 5,330 patients, from 520 unique records from the databases were included. Roxadustat significantly increased Hb levels during follow-up compared to the control group (Mean Difference [MD = 1.21 g/dL], 95% confidence interval [95% CI 0.45 to 1.97], I² = 99%, p = 0.0017). However, at weeks 24–28, the increase in Hb levels was not statistically significant (MD = 0.86 g/dL, 95% CI -0.11 to 1.83, I² = 99.4%, p = 0.0833). Iron-related parameters showed mixed results. Roxadustat was associated with a significant reduction in ferritin levels (MD = -38.54 ng/mL, 95% CI -68.21 to -8.87, I² = 84.1%, p = 0.0109). Conversely, Total Iron-Binding Capacity (TIBC) was significantly increased with Roxadustat treatment (MD = 20.33 μg/dL, 95% CI 1.15 to 39.51, I² = 98.5%, p = 0.0377). No significant difference was observed in serum iron (MD = 3.1 μg/dL, 95% CI -0.39 to 6.6, I² = 93.1%, p = 0.0820) and Transferrin Saturation (TSAT) levels (MD = -1.08%, 95% CI -2.42 to 0.26, I² = 40.1%, p = 0.1151) between the two groups. Subgroup analyses revealed that in placebo-controlled trials, Roxadustat significantly increased Hb levels at both weeks 24–28 and during follow-up. However, in trials comparing Roxadustat with ESAs, the changes in Hb levels were not significant at either time point. Roxadustat reduced ferritin but increased TIBC without significantly affecting free iron and TSAT levels compared to the control group in patients with NDD-CKD.