Anemic patients on hemodialysis (HD) respond well to roxadustat, an oral hypoxia-inducible factor prolyl hydroxylase (HIF-PHI) inhibitor, whether or not they are previously treated with erythropoiesis-stimulating agents (ESAs), according to results from separate phase 3 studies published in Therapeutic Apheresis and Dialysis.
In a study of ESA-naïve patients (NCT02780141), investigators randomly assigned 75 older Japanese patients to receive roxadustat (initial dose 50 or 70 mg, 3 times weekly) for up to 24 weeks. The other study (NCT02779764) included 164 older Japanese patients who received roxadustat after having previously received ESA treatment (ESA-converted group). The initial roxadustat dose was 70 or 100 mg, which was determined by the prior ESA dose, 3 times weekly for up to 52 weeks. Doses were titrated to maintain a target hemoglobin (Hb) of 10.0 to 12.0 g/dL.
Mean Hb was 10.93 g/dL at weeks 18 to 24 in both studies, and 11.11 g/dL at weeks 46 to 52 in the ESA-converted study. By 18 to 24 weeks, Hb had increased 2.26 g/dL among ESA-naïve patients and decreased 0.03 g/dL among ESA-converted patients, before increasing 0.12 g/dL at weeks 46 to 52 in ESA-converted patients.
Overall, 73.0% of ESA-naïve patients maintained their Hb within target at 18 to 24 weeks; 79.1% and 71.2% of ESA-converted patients maintained their Hb within target at 18 to 24 and 46 to 52 weeks, respectively, Tadao Akizawa, MD, PhD, of Showa University School of Medicine, in Tokyo, and colleagues reported. Roxadustat appeared effective in the presence of inflammation, according to a subgroup analysis. Other results supported decreased hepcidin and improved iron transport.
“Overall, these studies demonstrate that titrated roxadustat successfully treated anemia in both ESA-naïve and ESA-converted Japanese patients on hemodialysis,” Dr Akizawa’s team stated. The results may not be generalizable to other ethnicities, the investigators cautioned.
Nearly one-third of patients reported serious treatment emergency adverse events, and 4% of patients discontinued treatment. The most common adverse events included nasopharyngitis, contact dermatitis, shunt occlusion, constipation, shunt stenosis, hyperphosphatemia, diarrhea, vomiting, eczema, contusion, back pain, and insomnia.
Akizawa T, Ueno M, Shiga T, Reusch M. Oral roxadustat three times weekly in ESA-naïve and ESA-converted patients with anemia of chronic kidney disease on hemodialysis: Results from two phase 3 studies [published online December 31, 2019]. Ther Apher Dial. doi:10.1111/1744-9987.13468