Roxadustat Effective for Renal Anemia Regardless of Inflammation Status

Renal & Urology News
18 Nov, 2020 ,

According to 2 new studies presented at the American Society of Nephrology’s Kidney Week 2020 Reimagined, Roxadustat increases hemoglobin (Hb) levels in patients with chronic kidney disease even in the setting of inflammation. “Inflammation is a common cause of decreased responsiveness to erythropoiesis-stimulating agents,” Mohamed A. El-Shahawy, MD, MPh, MHA, from the Keck-USC School of Medicine in Los Angeles, California, stated. “Roxadustat, an oral hypoxia-inducible factor prolyl hydroxylase inhibitor, treats anemia by inducing endogenous erythropoietin production and increasing iron utilization via reducing hepcidin.”

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Roxadustat increases hemoglobin (Hb) levels in patients with chronic kidney disease even in the setting of inflammation, according to 2 new studies presented at the American Society of Nephrology’s Kidney Week 2020 Reimagined.

“Inflammation is a common cause of decreased responsiveness to erythropoiesis-stimulating agents,” Mohamed A. El-Shahawy, MD, MPh, MHA, from the Keck-USC School of Medicine in Los Angeles, California, stated. “Roxadustat, an oral hypoxia-inducible factor prolyl hydroxylase inhibitor, treats anemia by inducing endogenous erythropoietin production and increasing iron utilization via reducing hepcidin.”

His team’s analysis of pooled data from 3 dialysis trials (ROCKIES, SIERRAS, HIMALAYAS) demonstrated that both medications resulted in a least square (LS) mean increase in Hb levels from baseline at 28 to 52 weeks, but the increase was greater among roxadustat recipients. In an intent-to-treat analysis set of 3246 patients (1612 on roxadustat and 1634 on epoetin alfa), Hb level increased by 1.3 g/dL among roxadustat recipients compared with 1.0 g/dL among epoetin alfa recipients. Among patients with inflammation — defined as a high-sensitivity C-reactive protein (hsCRP) level above 5 mg/L — roxadustat-treated patients had an increase of 1.3 g/dL, whereas the epoetin alfa group had an increase of 0.9 g/dL. The mean increase in Hb level among patients without inflammation was 1.3 g/dL in the roxadustat group and 1.1 g/dL in the epoetin alfa recipients. All the differences between the groups were statistically significant. The results were similar across quintiles of hsCRP.

Mean weekly roxadustat doses at week 24 did not change significantly across baseline hsCRP quintiles: 4.1, 3.5, 3.6, 3.5, and 3.7 mg/kg among patients in quintiles 1, 2, 3, 4, and 5, respectively. In contrast, higher doses of epoetin alfa were required for patients  with the highest hsCRP level (greater than 13.56 mg/dL). Patients in the highest quintile of hsCRP were less iron replete than patients with lower quintiles, the investigators noted.

Carol A. Pollock, MBBS, PhD, of the University of Sydney in Sydney, Australia, and colleagues found similar results in their pooled analysis of 3 trials (OLYMPUS, ALPS, ANDES) that compared roxadustat with placebo in patients with nondialysis-dependent chronic kidney disease.

In an intent-to-treat analysis set that included 2960 patients, roxadustat increased Hb levels significantly compared with placebo. At weeks 28 to 52, roxadustat recipients experienced an LS mean increase in Hb level of 1.92 g/dL from baseline compared with an increase of 0.41 g/dL in the placebo arm. Results were similar regardless of inflammation status. As in the dialysis studies, higher baseline hsCRP levels did not result in increases in roxadustat doses.

Of note, 2 other studies presented at Kidney Week found that roxadustat improves iron homeostasis by increasing both serum iron and iron-carrying capacity, without the need for regular intravenous iron supplementati