Post Hoc Analysis: Factors Affecting Doses of Roxadustat versus Darbepoetin Alfa

Roxadustat is an oral hypoxia-inducible factor prolyl hydroxylase inhibitor for the treatment of anemia in chronic kidney disease (CKD). Tadao Akizawa, MD, PhD, and colleagues reported results of a post hoc analysis of a Japanese, open-label, partially randomized, phase 3 study in nondialysis dependent (NDD) CKD patients treated with traditional erythropoiesis-stimulating agents (ESAs). Results were reported online in the American Journal of Nephrology [].

The analysis assessed dosing trends of roxadustat and darbepoetin alfa (DA) required to maintain target hemoglobin (Hb) concentrations in patients with risk factors associated with ESA hyporesponsiveness. The 1517-CL-0310 study (NCT02988973) demonstrated the noninferiority of roxadustat to DAS for change from baseline in average Hb levels week 18 to 24. Patients in the study had used human recombinant erythropoietin or darbepoetin alfa before conversion were randomized to receive either roxadustat or DA.

Study end points were the average allocated dose of roxadustat and DA per administration in the last 6 weeks (AAD/6W), assessed by subgroups known to be associated with ESA hyporesponsiveness. The analysis of variance was performed by the treatment group to test the influence of subgroup factors on the AAD/6W of study drug. The researchers calculated the ratios between the mean AAD/6W in each subgroup category and the within-arm mean AAD/6W.

A total of 262 patients were randomized to either the roxadustat or DA comparative group and received treatment with roxadustat (n=131) or DA, (n=131). Higher mean doses of both roxadustat and DA were required in the highest quartile of ESA resistance (63.15 mg [P=.003] and 47.33 [P<.001], respectively). The lowest doses for both roxadustat and DA were administered to patients with adequate iron repletion (45.54 mg and 28.13 mg, respectively).

There were associations between high-sensitivity C-reactive protein ≥28.57 nmol/L and estimated glomerular filtration rate <15 mL/min/1.73 m2 and requiring  higher dose of DA but not of roxadustat.

In conclusion, the researchers said, “The roxadustat dose required to maintain target hemoglobin in NDD patients in Japan with anemia of CKD relative to DA dose may not be impacted by low-grade inflammation. Roxadustat may be beneficial for ESA-hyporesponsive NDD CKD patients.”