The risk of developing ophthalmic abnormalities appears no higher with roxadustat compared with darbepoetin alfa in patients with chronic kidney disease (CKD) receiving and not receiving dialysis, investigators reported at Kidney Week 2020 Reimagined, the virtual meeting sponsored by the American Society of Nephrology.
Roxadustat is an oral hypoxia-inducible factor (HIF) prolyl hydroxylase inhibitor in late-stage development for anemia of CKD. Nonclinical data have suggested that HIF stabilization may promote retinal angiogenesis via increases in vascular endothelial growth factor expression, thereby increasing the risk for hypoxia-induced retinal hemorrhages and macular edema, Quan Dong Nguyen, MD, MSc, of Byers Eye Institute, Stanford School of Medicine, in Stanford, California, explained.
His team analyzed ophthalmological assessments (funduscopic photograph and optical coherence tomography) from 2 phase 3 trials of roxadustat vs darbepoetin involving 302 dialysis-dependent (DD) and 262 nondialysis-dependent (NDD) patients with CKD. To be included in the study, patients needed to have hemoglobin levels within 10 to 12 g/dL and to be iron replete and receiving treatment with erythropoiesis-stimulating agents prior to randomization.
The total number of retinal hemorrhages did not change meaningfully from baseline to week 24 or end of treatment among DD-CKD (mean 0.2 vs 0.3) or NDD-CKD (-1.6 vs -1.6) patients taking roxadustat vs darbepoetin, respectively, Dr Nguyen reported.
New or worsening retinal hemorrhages were mostly comparable between the roxadustat and darbepoetin groups among DD-CKD (23.9% vs 29.0%) at the end of treatment and NDD-CKD (21.5% vs 34.4%) patients at the end of week 24, respectively. The same pattern was observed across important subgroups. Among patients with no retinal hemorrhages at baseline, the rates of new or worsening retinal hemorrhages were 13.8% vs 18.8% among DD-CKD patients at the end of treatment and 6.5% vs 20.8% among NDD-CKD patients at the end of week 24, respectively. Among patients with 1 or more retinal hemorrhages at baseline, the rates of new or worsening retinal hemorrhages were 43.8% vs 49.0% among DD-CKD patients at the end of treatment and 37.3% vs 51.8% among NDD-CKD patients at the end of week 24, respectively.
Among patients free of diabetes, lower rates of new or worsening retinal hemorrhages were observed at the end of treatment in the roxadustat vs darbepoetin group receiving dialysis (13.3% vs 23.2%) and at the end of week 24 those not receiving dialysis (7.0% vs 25.8%), respectively. Among patients with diabetes, comparable rates were observed at the end of treatment in the roxadustat vs darbepoetin group receiving dialysis (42.3% vs 40.0%) and at the end of week 24 among those not receiving dialysis (34.4% vs 42.4%), respectively.
“Data from this analysis do not support the hypothesis that HIF stabilization associated with administration of roxadustat increases the risk of retinal hemorrhage,” Dr Nguyen concluded.
In addition, he reported that no clinically meaningful changes in macular edema events, including retinal thickness, visual acuity, hard exudates, cotton wool spots, or the presence of intraretinal or subretinal fluid over 24 weeks or until end of treatment in any group.
Disclosure: This clinical trial was supported by Astellas Pharma. Please see the original reference for a full list of authors’ disclosures.
Nguyen QD, Sepah YJ, Yamaguchi Y, et al. Ophthalmological effects of roxadustat in the treatment of anemia in dialysis-dependent and non-dialysis-dependent CKD patients: findings from two phase 3 studies. Presented at: Kidney Week 2020 Reimagined, October 19-25, 2020. Poster PO0267.